胡芦巴丸及灰兜巴抗氧化应激治疗糖尿病肾病的机理研究
|
摘要
第一部分从PKCα-NADPH氧化酶信号通路探讨胡芦巴丸及其单味药治疗大鼠糖尿病肾病的分子机制
目的
探讨胡芦巴丸及其单味药抗氧化应激治疗大鼠糖尿病肾病(DN)的分子机制。
方法
采用高糖高脂饮食和尾静脉小剂量链脲佐菌素(STZ)的方法建立大鼠DN模型,将大鼠随机分为模型组、胡芦巴组、补骨脂组、胡芦巴丸组、卡托普利组,另设正常对照组,给予相应药物灌胃治疗16周,检测血糖、血脂、血尿素氮(BUN)、血肌酐(SCr)、尿24小时总蛋白、尿24小时白蛋白水平,光镜下观察肾脏形态学改变(HE染色、PAS染色、Masson染色),电镜下观察肾脏超微结构改变,DHE染色法评估肾脏组织超氧阴离子水平,浓度比色法检测肾组织烟酰胺腺嘌呤二核苷酸磷酸(NADPH)活性,Western blot检测肾脏组织p47phox、磷酸化蛋白激酶C-α(PKC-α)、纤粘蛋白(FN)的蛋白表达水平,实时荧光定量PCR(RT-PCR)检测肾脏组织p47phox、 PKC-α、的mRNA表达水平。结果
与正常组比较,模型组大鼠血糖升高、血脂紊乱,24小时尿总蛋白及白蛋白水平均明显升高(P<0.01),肾小球体积增大、肾小球纤维化、细胞外基质增生、足细胞足突融合；与模型组比较,胡芦巴、补骨脂、胡芦巴丸组大鼠血糖水平下降,血脂紊乱改善,24小时尿总蛋白及白蛋白水平均明显下降(P<0.01),上述肾脏病理学改变明显减轻。与正常组比较,模型组大鼠肾组织DHE荧光水平明显升高,肾组织NADPH氧化酶活性、p47phox蛋白及mRNA表达水平、磷酸化PKC-α、FN蛋白表达水平均明显升高(P<0.01)；与模型组比较,胡芦巴、补骨脂、胡芦巴丸组大鼠肾组织DHE荧光水平明显降低,肾组织NADPH氧化酶活性、p47phox蛋白及mRNA表达水平磷酸化PKC-α、FN蛋白表达水平均明显降低(P<0.01)。与胡芦巴丸组比较,胡芦巴、补骨脂组大鼠肾组织NADPH活性、p47phox蛋白及mRNA表达水平、肾组织磷酸化PKC-α、FN蛋白表达均增加(P<0.01,P<0.05)
结论
胡芦巴丸及其单味药均可有效治疗大鼠糖尿病肾病,其机制可能与抑制肾组织PKCα-NADPH氧化酶信号通路减轻氧化应激有关,胡芦巴丸改善肾组织氧化应激优于单味药。
第二部分灰兜巴抑制肾组织NADPH氧化酶活性治疗大鼠糖尿病肾病的机理研究
目的
探讨灰兜巴对大鼠糖尿病肾病的防治作用及机制。
方法
采用高糖高脂饮食和小剂量链脲佐菌素(STZ)尾静脉注射建立大鼠糖尿病肾病模型,将大鼠随机分为模型组、灰兜巴组、卡托普利组,另设正常对照组,给予相应药物灌胃治疗12周,检测血糖、血脂、尿素氮(BUN)、肌酐(SCr)、血清丙二醛(MDA)、24小尿微量白蛋白(UALB)水平,观察肾组织形态学改变,浓度比色法检测肾组织烟酰胺腺嘌呤二核苷酸磷酸(NADPH)(?)舌性,Western blot检测肾组织NADPH氧化酶亚单位p47phox蛋白的表达。结果
与正常组比较,模型组大鼠空腹及餐后血糖、血脂紊乱,血清MDA、BUN、SCr、24hUALB均明显升高(P<0.01),肾小球体积增大,系膜区及细胞外基质增生(P<0.01),肾组织NADPH活性、p47phox蛋白表达明显升高(P<0.01)；与模型组比较,灰兜巴组大鼠空腹及餐后血糖明显降低,血脂紊乱改善,血清MDA、BUN、SCr和24hUALB明显降低(P<0.01),肾小球体积近乎正常,系膜区、基质未见增生,肾组织NADPH(?)舌性、p47phox蛋白表达明显降低(P<0.01)。
结论
灰兜巴可明显改善糖尿病肾病大鼠糖脂代谢紊乱,对糖尿病肾病具有防治作用。其机制可能与下调肾组织NADPH(?)舌性减轻氧化应激有关。
第三部分绝经后骨质疏松症患者骨密度与性激素水平、氧化应激相关指标的相关性分析
目的
分析绝经后骨质疏松症(PMOP)患者骨密度(BMD)与性激素水平、氧化应激相关指标的相关性。
方法
入选58例PMOP患者,行双能X线吸收仪(DXA)检测骨密度(BMD),同时进行人体学特征、血清性激素水平和氧化应激相关指标丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)的检测,分析BMD与上述各指标的相关性。
结果
PMOP患者BMD仅与身高呈正相关,相关系数分别为腰椎r=0.390、髋关节r=0.357(P<0.01),BMD与血清性激素水平、氧化应激相关指标均无相关性。
结论
PMOP患者骨密度(BMD)与性激素水平、氧化应激相关指标之间无明显相关性,需寻找更有价值的相关联因素。
Section Ⅰ Hu-lu-ba-wan and its Single Components Attenuate Rat Diabetic Nephropathy through PKCa-NADPH Oxidase Signaling Pathway
Objective
The aim of this study was to explore the effect of Hu-lu-ba-wan (HLBW) and its single components on diabetic nephropathy (DN) in type2diabetic rats and to investigate its possible oxidative stress-against mechanism.
Methods
The rat model of DN was established by feeding with a high-fat diet and intravenous injection of small doses of streptozotocin. DN rats were randomized into the diabetic control group, TFG treated group, PC treated group, HLBW treated group and Captopril treated group. Meanwhile, eight rats were selected randomly as the normal group. Rats in the above treatment groups were administered with corresponding therapy intragastrically for16weeks. Blood glucose level, lipid profile, blood urea nitrogen (BUN), serum creatinine (SCr) concentrations, and total urinary protein and albumin content for24hours were examined. Renal morphology changes were evaluated by the staining with hematoxylin and eosin (HE), periodic acid-schiff (PAS), aniline blue (AB) and the observation under transmission electron microscope. Renal superoxide anion levels were assessed by dihydroethidium (DHE) fluorescence staining. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH), the protein expressions of p47phox, phosphorylated PKC-a and fibronectin, the mRNA expressions of p47phox and PKC-a in renal tissue were also determined.
Results
Compared with the normal group, the rats in the model group showed remarkable glomerular expansion and fibrosis. extracellular matrix (ECM) accumulation, effacement of the foot processes of podocytes. Blood BG, TG, TC, LDL-C, BUN, SCr concentrations and urinary total protein and albumin content were also significantly increased. Meanwhile, diabetic rats showed the elevation of DHE fluorescence level, the NADPH oxidase activity, the P47phox protein and mRNA expression, and the phosphorylated PKC-a and fibronectin protein expression in renal tissues (P<0.01). However. HLBW and its single components treatment effectively reversed the above biochemical changes in diabetic rats (P<0.01). The addition of HLBW and its single components also reduced DHE fluorescence level, NADPH oxidase activity, the protein and mRNA expression of P47phox, and the protein expression of phosphorylated PKC-a and fibronectin in renal tissues (P<0.01). Compared with HLBW treated group, rats in TFG treated group and PC treated group showed elevated NADPH oxidase activity, the protein and mRNA expressions of p47phox. and the protein expression of phosphorylated PKC-a in renal tissues (P<0.01,P<0.05).
Conclusion
These results suggest that HLBW and its single components are effective in the treatment of DN in type2diabetic rats. The mechanism may be related to the reduction of renal oxidative stress via PKCa-NADPH oxidase signaling pathway on the administration of HLBW and its single components. The attenuating renal oxidative stress efficacy of composite prescription (HLBW) is superior to that of simple prescription (TFG or PC).
Section Ⅱ Huidouba Attenuates Rat Diabetic Nephropathy by Inhibition of NAPDH Oxidase Activity
Objective
To investigate the mechanism and effect of Huidouba in the treatment of diabetic nephropathy in rats.
Methods
The rat model of diabetic nephropathy (DN) was established by feeding with a high-fat diet and intravenous injection of small doses of streptozotocin. DN rats were randomized into the diabetic control group, Huidouba polysaccharides treated group and Captopril treated group. Meanwhile, seven rats were selected randomly as the normal group. Rats in the above treatment groups were administered with corresponding therapy intragastrically for12weeks. Renal histological assessment was observed. Blood glucose (BG), blood lipid (TG, TC, LDL-C, HDL-C), malondialdehyde (MDA), blood urea nitrogen (BUN), serum creatinine (SCr) concentrations, and24hours urinary microalbumin (UALB) content were examined. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and the protein expressions of P47phox in renal tissues were also determined.
Results
Compared with the normal group, the rats in the model group showed remarkable glomerular hypertrophy. Blood BG, TG, TC, LDL-C, MDA, BUN, SCr concentrations and UALB content were also significantly increased with the elevation of the NADPH oxidase activity and the P47phox protein expression in renal tissues (P<0.01). However, Huidouba treatment effectively reversed the above biochemical changes in diabetic rats. The addition of Huidouba also reduced NADPH oxidase activity and the protein expression of P47phox in renal tissues (P<0.01).
Conclusion
It is concluded that Huidouba is effective on ameliorating glucose and lipid metabolism disturbances and renal injury in diabetic rats. The mechanism may be related to reducing oxidative stress via inhibiting the activity of NADPH oxidase.
Section Ⅲ Correlation of Bone Mineral Density with Sexual Hormones and Oxidative Stress in Patients with Postmenopausal Osteoporosis
Objective
To analyze the correlation of bone mineral density (BMD) with sexual hormones and oxidative stress in Patients with postmenopausal osteoporosis (PMOP).
Methods
Fifty-eight postmenopausal osteoporosis patients were selected. BMD was quantified by dual energy X-ray absorptiometry (DXA). Anthropometric features and serum sexual hormones and oxidative stress parameters were tested. Correlations between BMD and other items were analyzed.
Results
We found that only height was significantly correlated with BMD (r=0.390, r=0.357)(P<0.01). Serum sexual hormones and oxidative stress parameters were not correlated with BMD(P>0.05).
Conclusion
It is concluded that there is no correlation of BMD with sexual hormones and oxidative stress in patients with PMOP. More effective related factors are needed to be identified.
目的
探讨胡芦巴丸及其单味药抗氧化应激治疗大鼠糖尿病肾病(DN)的分子机制。
方法
采用高糖高脂饮食和尾静脉小剂量链脲佐菌素(STZ)的方法建立大鼠DN模型,将大鼠随机分为模型组、胡芦巴组、补骨脂组、胡芦巴丸组、卡托普利组,另设正常对照组,给予相应药物灌胃治疗16周,检测血糖、血脂、血尿素氮(BUN)、血肌酐(SCr)、尿24小时总蛋白、尿24小时白蛋白水平,光镜下观察肾脏形态学改变(HE染色、PAS染色、Masson染色),电镜下观察肾脏超微结构改变,DHE染色法评估肾脏组织超氧阴离子水平,浓度比色法检测肾组织烟酰胺腺嘌呤二核苷酸磷酸(NADPH)活性,Western blot检测肾脏组织p47phox、磷酸化蛋白激酶C-α(PKC-α)、纤粘蛋白(FN)的蛋白表达水平,实时荧光定量PCR(RT-PCR)检测肾脏组织p47phox、 PKC-α、的mRNA表达水平。结果
与正常组比较,模型组大鼠血糖升高、血脂紊乱,24小时尿总蛋白及白蛋白水平均明显升高(P<0.01),肾小球体积增大、肾小球纤维化、细胞外基质增生、足细胞足突融合；与模型组比较,胡芦巴、补骨脂、胡芦巴丸组大鼠血糖水平下降,血脂紊乱改善,24小时尿总蛋白及白蛋白水平均明显下降(P<0.01),上述肾脏病理学改变明显减轻。与正常组比较,模型组大鼠肾组织DHE荧光水平明显升高,肾组织NADPH氧化酶活性、p47phox蛋白及mRNA表达水平、磷酸化PKC-α、FN蛋白表达水平均明显升高(P<0.01)；与模型组比较,胡芦巴、补骨脂、胡芦巴丸组大鼠肾组织DHE荧光水平明显降低,肾组织NADPH氧化酶活性、p47phox蛋白及mRNA表达水平磷酸化PKC-α、FN蛋白表达水平均明显降低(P<0.01)。与胡芦巴丸组比较,胡芦巴、补骨脂组大鼠肾组织NADPH活性、p47phox蛋白及mRNA表达水平、肾组织磷酸化PKC-α、FN蛋白表达均增加(P<0.01,P<0.05)
结论
胡芦巴丸及其单味药均可有效治疗大鼠糖尿病肾病,其机制可能与抑制肾组织PKCα-NADPH氧化酶信号通路减轻氧化应激有关,胡芦巴丸改善肾组织氧化应激优于单味药。
第二部分灰兜巴抑制肾组织NADPH氧化酶活性治疗大鼠糖尿病肾病的机理研究
目的
探讨灰兜巴对大鼠糖尿病肾病的防治作用及机制。
方法
采用高糖高脂饮食和小剂量链脲佐菌素(STZ)尾静脉注射建立大鼠糖尿病肾病模型,将大鼠随机分为模型组、灰兜巴组、卡托普利组,另设正常对照组,给予相应药物灌胃治疗12周,检测血糖、血脂、尿素氮(BUN)、肌酐(SCr)、血清丙二醛(MDA)、24小尿微量白蛋白(UALB)水平,观察肾组织形态学改变,浓度比色法检测肾组织烟酰胺腺嘌呤二核苷酸磷酸(NADPH)(?)舌性,Western blot检测肾组织NADPH氧化酶亚单位p47phox蛋白的表达。结果
与正常组比较,模型组大鼠空腹及餐后血糖、血脂紊乱,血清MDA、BUN、SCr、24hUALB均明显升高(P<0.01),肾小球体积增大,系膜区及细胞外基质增生(P<0.01),肾组织NADPH活性、p47phox蛋白表达明显升高(P<0.01)；与模型组比较,灰兜巴组大鼠空腹及餐后血糖明显降低,血脂紊乱改善,血清MDA、BUN、SCr和24hUALB明显降低(P<0.01),肾小球体积近乎正常,系膜区、基质未见增生,肾组织NADPH(?)舌性、p47phox蛋白表达明显降低(P<0.01)。
结论
灰兜巴可明显改善糖尿病肾病大鼠糖脂代谢紊乱,对糖尿病肾病具有防治作用。其机制可能与下调肾组织NADPH(?)舌性减轻氧化应激有关。
第三部分绝经后骨质疏松症患者骨密度与性激素水平、氧化应激相关指标的相关性分析
目的
分析绝经后骨质疏松症(PMOP)患者骨密度(BMD)与性激素水平、氧化应激相关指标的相关性。
方法
入选58例PMOP患者,行双能X线吸收仪(DXA)检测骨密度(BMD),同时进行人体学特征、血清性激素水平和氧化应激相关指标丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)的检测,分析BMD与上述各指标的相关性。
结果
PMOP患者BMD仅与身高呈正相关,相关系数分别为腰椎r=0.390、髋关节r=0.357(P<0.01),BMD与血清性激素水平、氧化应激相关指标均无相关性。
结论
PMOP患者骨密度(BMD)与性激素水平、氧化应激相关指标之间无明显相关性,需寻找更有价值的相关联因素。
Section Ⅰ Hu-lu-ba-wan and its Single Components Attenuate Rat Diabetic Nephropathy through PKCa-NADPH Oxidase Signaling Pathway
Objective
The aim of this study was to explore the effect of Hu-lu-ba-wan (HLBW) and its single components on diabetic nephropathy (DN) in type2diabetic rats and to investigate its possible oxidative stress-against mechanism.
Methods
The rat model of DN was established by feeding with a high-fat diet and intravenous injection of small doses of streptozotocin. DN rats were randomized into the diabetic control group, TFG treated group, PC treated group, HLBW treated group and Captopril treated group. Meanwhile, eight rats were selected randomly as the normal group. Rats in the above treatment groups were administered with corresponding therapy intragastrically for16weeks. Blood glucose level, lipid profile, blood urea nitrogen (BUN), serum creatinine (SCr) concentrations, and total urinary protein and albumin content for24hours were examined. Renal morphology changes were evaluated by the staining with hematoxylin and eosin (HE), periodic acid-schiff (PAS), aniline blue (AB) and the observation under transmission electron microscope. Renal superoxide anion levels were assessed by dihydroethidium (DHE) fluorescence staining. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH), the protein expressions of p47phox, phosphorylated PKC-a and fibronectin, the mRNA expressions of p47phox and PKC-a in renal tissue were also determined.
Results
Compared with the normal group, the rats in the model group showed remarkable glomerular expansion and fibrosis. extracellular matrix (ECM) accumulation, effacement of the foot processes of podocytes. Blood BG, TG, TC, LDL-C, BUN, SCr concentrations and urinary total protein and albumin content were also significantly increased. Meanwhile, diabetic rats showed the elevation of DHE fluorescence level, the NADPH oxidase activity, the P47phox protein and mRNA expression, and the phosphorylated PKC-a and fibronectin protein expression in renal tissues (P<0.01). However. HLBW and its single components treatment effectively reversed the above biochemical changes in diabetic rats (P<0.01). The addition of HLBW and its single components also reduced DHE fluorescence level, NADPH oxidase activity, the protein and mRNA expression of P47phox, and the protein expression of phosphorylated PKC-a and fibronectin in renal tissues (P<0.01). Compared with HLBW treated group, rats in TFG treated group and PC treated group showed elevated NADPH oxidase activity, the protein and mRNA expressions of p47phox. and the protein expression of phosphorylated PKC-a in renal tissues (P<0.01,P<0.05).
Conclusion
These results suggest that HLBW and its single components are effective in the treatment of DN in type2diabetic rats. The mechanism may be related to the reduction of renal oxidative stress via PKCa-NADPH oxidase signaling pathway on the administration of HLBW and its single components. The attenuating renal oxidative stress efficacy of composite prescription (HLBW) is superior to that of simple prescription (TFG or PC).
Section Ⅱ Huidouba Attenuates Rat Diabetic Nephropathy by Inhibition of NAPDH Oxidase Activity
Objective
To investigate the mechanism and effect of Huidouba in the treatment of diabetic nephropathy in rats.
Methods
The rat model of diabetic nephropathy (DN) was established by feeding with a high-fat diet and intravenous injection of small doses of streptozotocin. DN rats were randomized into the diabetic control group, Huidouba polysaccharides treated group and Captopril treated group. Meanwhile, seven rats were selected randomly as the normal group. Rats in the above treatment groups were administered with corresponding therapy intragastrically for12weeks. Renal histological assessment was observed. Blood glucose (BG), blood lipid (TG, TC, LDL-C, HDL-C), malondialdehyde (MDA), blood urea nitrogen (BUN), serum creatinine (SCr) concentrations, and24hours urinary microalbumin (UALB) content were examined. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and the protein expressions of P47phox in renal tissues were also determined.
Results
Compared with the normal group, the rats in the model group showed remarkable glomerular hypertrophy. Blood BG, TG, TC, LDL-C, MDA, BUN, SCr concentrations and UALB content were also significantly increased with the elevation of the NADPH oxidase activity and the P47phox protein expression in renal tissues (P<0.01). However, Huidouba treatment effectively reversed the above biochemical changes in diabetic rats. The addition of Huidouba also reduced NADPH oxidase activity and the protein expression of P47phox in renal tissues (P<0.01).
Conclusion
It is concluded that Huidouba is effective on ameliorating glucose and lipid metabolism disturbances and renal injury in diabetic rats. The mechanism may be related to reducing oxidative stress via inhibiting the activity of NADPH oxidase.
Section Ⅲ Correlation of Bone Mineral Density with Sexual Hormones and Oxidative Stress in Patients with Postmenopausal Osteoporosis
Objective
To analyze the correlation of bone mineral density (BMD) with sexual hormones and oxidative stress in Patients with postmenopausal osteoporosis (PMOP).
Methods
Fifty-eight postmenopausal osteoporosis patients were selected. BMD was quantified by dual energy X-ray absorptiometry (DXA). Anthropometric features and serum sexual hormones and oxidative stress parameters were tested. Correlations between BMD and other items were analyzed.
Results
We found that only height was significantly correlated with BMD (r=0.390, r=0.357)(P<0.01). Serum sexual hormones and oxidative stress parameters were not correlated with BMD(P>0.05).
Conclusion
It is concluded that there is no correlation of BMD with sexual hormones and oxidative stress in patients with PMOP. More effective related factors are needed to be identified.
引文
[1]Yang WY, Lu JM, Weng JP, et al. Prevalence of diabetes among men and women in China [J]. N Engl J Med.2012,362(12):1090-1101.
[2]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21 (2):296-309.
[3]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[4]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91 (2):261-270.
[5]Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury:activation of polyol pathway and oxidative stress responsive signaling cascades [J]. Chem Biol Interact. 2009,181 (3):297-308.
[6]Manna P, Sinha M, Sil PC. Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction [J]. Amino Acids. 2009,36(3):417-428.
[7]Lu FR, Shen L, Qin Y, et al. Clinical observation on Trigonella foenum-graecum L. total saponins in combination with sulphanylureas in the treatment of type 2 diabetes mellitus [J]. Chin J Integr Med.2008,14(1):56-60.
[8]Anchalee S, Catherine JF, Alan BRT, et al. The modifying effects of galactomannan from canadian-grown fenugreek (Trigonella foenum-graecum L.) on the glycemic and lipidemic status in rats [J]. J Clin Biochem Nutr. 2008,43(3):167-174.
[9]Broca C, Breil V, Cruciani-Guglielmacci C, et al. Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat [J]. Am J Physiol Endocrinol Metab.2004,287(3):E463-E471.
[10]Jette L, Harvey L, Eugeni K, et al.4-Hydroxyisoleucine:a plant-derived treatment for metabolic syndrome [J]. Curr Opin Investig Drugs. 2009,10(4):353.
[11]Bapat K, Chintalwar GJ, Pandey U, et al. Prepration and in vitro evaluation of radioiodinated bakuchiol as an antitumour agent [J]. Appl Radiat Isot. 2005,62(3):389-393.
[12]Khatune NA, Islam ME, Haque ME, et al. Antibacterial compounds from seeds of Psoralea corylifolia L [J]. Fitoterapia.2004,75(2):228-230.
[13]Xiong Z, Wang D, Xu Y, et al. Osteoblastic differentiation bioassay and its application to investigating the activity of fractions and compounds from Psoralea corylifolia L [J]. Pharmazie.2003,58(12):925-928.
[14]Uma NT, Deepak C. The plant extracts of Momordica charantia and Trigonella foenum graecum have antioxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus [J]. Oxid Med Cell Longev. 2009,2(5):290-296.
[15]Sangeetha R. Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim [J]. Indian J Pharm Sci.2010,72(1):116-118.
[16]Soon YT, Jan G, Kim PW, et al. Psoralea corylifolia L. Inhibits Mitochondrial Complex I and Proteasome Activities in SH-SY5Y Cells [J]. Ann N Y Acad Sci.2007,1100(1):486-496.
[17]Sumira J, Talat P, Siddiqi TO, et al. Anti-oxidant modulation in response to gamma radiation induced oxidative stress in developing seedlings of Psoralea corylifolia L[J]. J Environ Radioact.2012,113(1):142-149.
[18]Thakran S, Siddiqui MR, Baquer NZ. Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats [J]. Mol Cell Biochem.2004,266(1-2):151-159.
[19]Kim YC, Oh H, Kim BS, et al. In vitro Protein Tyrosine Phosphatase IB Inhibitory Phenols from the Seeds of Psoralea corylifolia [J]. Planta Med. 2005,71(1):87-89.
[20]Helena P, Charles WL, Shyamali B, et al. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures [J]. J Cereb Blood Flow Metab.2012,32(6):1024-1034.
[21]Hari H, Toyoshi I, Yasutaka M, et al. GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases [J]. Metabolism.2012,61(10):1422-1434.
[22]Osamu K, Kazuhide U, Hisayo K, et al. Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells [J]. Clin Exp Nephrol.2009,13(1):15-24.
[23]Jesys AC, Elizabeth AZ, Robert C, et al. Uncoupling protein-2 expression and effects on mitochondrial membrane potential and oxidant stress in heart tissue [J]. Transl Res.2012,159(5):383-390.
[24]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91(2):261-270.
[25]Ralf PB, Jorg K. Vascular NADPH oxidases:molecular mechanisms of activation [J]. Cardiovasc Res.2005,65(1):16-27.
[26]Seiya S, Harukiyo K, Minoru T, et al. Halofuginone prevents extracellular matrix deposition in diabetic nephropathy [J]. Biochem Biophys Res Commun. 2009,379(2):411-416.
[27]Lin CC, Lin LT, Yen MH, et al. Renal Protective Effect of Xiao-Chai-Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice [J]. Evid Based Complement Alternat Med.2012,2012(1):984024.
[28]Larissa P, Mayara SG, Carolina BAR, et al. The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat [J]. Eur J Pharmacol.2012,678(1-3):15-25.
[29]Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes [J]. Diabetes.2008,57(6):1446-1454.
[30]Toba H, Sawai N, Morishita M, et al. Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat [J]. Eur J Pharmacol. 2009,612(1-3):106-114.
[1]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21(2):296-309.
[2]胡善联,刘国恩,许樟荣等.我国糖尿病流行病学和疾病经济负担研究现状[J].中国卫生经济,2008,227(8)：5-8.
[3]Yang WY, Lu JM, Weng JP, et al. Prevalence of diabetes among men and women in China [J]. N Engl J Med.2012,362(12):1090-1101.
[4]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[5]廖二元,莫朝晖.内分泌学(第2版)[M].北京：人民卫生出版社,2007：1448-1449.
[6]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91(2):261-270.
[7]Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury:activation of polyol pathway and oxidative stress responsive signaling cascades [J]. Chem Biol Interact. 2009,181(3):297-308.
[8]Manna P, Sinha M, Sil PC. Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction [J]. Amino Acids. 2009,36(3):417-428.
[9]宋根萍.灰兜巴有效成分的提取方法：中国,CN101380339A[P]. 2009-03-11.
[10]刘艳,周慧,滕利荣.灰兜巴多糖的提取及其降血糖活性的研究[D].吉林大学,2009：4.
[11]赵劲航,田淑琴.中药复方灰兜巴对糖尿病治疗作用研究[J].西南民族大学学报·自然科学版,2008,34(6)：1186-1188.
[12]赵敏,宋静静,王贞佐等.复方灰兜巴预防及治疗糖尿病的实验研究[J].食品及药物,2011,13(7)：254-257.
[13]彭亮,李知敏.灰兜巴抗糖尿病作用的实验研究[J].时珍国医国药,2010,21(12)：3060-3061.
[14]彭亮,李知敏,徐玲.灰兜巴提取物体外清除自由基活性的研究[J].安徽农业科学,2010,38(14)：7343-7344,7347.
[15]黄琳,陆付耳,杨小玉等.黄连解毒汤对胰岛素抵抗大鼠肝脏线粒体氧化应激的影响[J].中国中西医结合杂志,2008,28(8)：725-728.
[16]Ralf PB, Jorg K. Vascular NADPH oxidases:molecular mechanisms of activation [J]. Cardiovasc Res.2005,65(1):16-27.
[17]Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes [J]. Diabetes.2008,57(6):1446-1454.
[18]Toba H, Sawai N, Morishita M, et al. Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat [J]. Eur J Pharmacol. 2009,612(1-3):106-114.
[1]Cole ZA, Dennison EM, Cooper C. Osteoporosis epidemiology update [J]. Curr Rheumatol Rep.2008,10(2):92-96.
[2]薛延.骨质疏松症的流行病学概况[J].新医学,2007,38(1)：7-8.
[3]Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States,2005-2025 [J]. J Bone Miner Res.2007,22(3):465-475.
[4]章振林.骨质疏松流行病学现状[J].中华医学杂志,2009,89(42)：2953-2955.
[5]Lydick E, Cook K, Turpin J, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density [J]. Am J Manag Care.1998,4(l):37-48.
[6]Kanis J. Assessment of osteoporosis at the primary health care level [R]. World Health Organization Collaborating Centre For Metabolic Bone Diseases. University Of Sheffield, UK:2008.
[7]Ben SW, Chevallier T, Zegels B, et al. Development and assessment of the Osteoporosis Index of Risk (OSIRIS) to facilitate selection of women for bone densitometry [J]. Gynecol Endocrinol.2002,16(3):245-250.
[8]张菊英,吴涛,杨定焯等.中国大陆地区妇女骨质疏松筛选工具探讨[J].中国修复重建外科杂志,2007,21(1)：86-89.
[9]Cadarette SM, Jaglal SB, Kreiger N, et al. Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry [J]. CMAJ.2000,162(9):1289-1294.
[10]Vikram ST, Timothy C, Isaac M. Exploiting the antioxidant potential of a common vitamin:Could vitamin C prevent postmenopausal osteoporosis [J]? J Obstet Gynaecol Res.2012,38(1):253-257.
[11]Maryam SH, Paul NC, Angela MC. Effects of vitamin E on bone turnover markers among US postmenopausal women [J]. J Bone Miner Res. 2012,27(6):1368-1380.
[12]Serap Y, Ozgun S, Ulku C, et al. Strontium ranelate treatment improves oxidative damage in osteoporotic rat model [J]. Pharmacol Rep. 2012,64(2):396-402.
[13]Zhang YB, Zhong ZM, Hou G, et al. Involvement of Oxidative Stress in Age-Related Bone Loss [J]. J Surg Res.2011,169(1):e37-e42.
[14]WHO:Guidelines for Preclinical Evaluation And Clinical Trials In Osteoporosis [R]. Geneva:1998.
[15]田峰,谢雁鸣.绝经后骨质疏松症危险因素、预测模型和筛检工具研究[J].中国骨质疏松杂志,2011,17(2)：166-171.
[16]Rossouw JE, Anderson GL, Prentice RL, et al. Risk and benefit of estrogen plus progestin in healthy postmenopausal women:principal results from the women's health initiative randomized controlled trial [J]. JAMA. 2002,288(3):321.
[17]Lin JT, Lane JM. Osteoporosis:A review [J]. Clin Orthop Relat Res. 2004,425(1):126.
[18]单鹏飞,伍贤平,廖二元等.女性骨代谢转换生化指标和骨密度随龄变化及其相互关系[J].中华老年医学杂志,2005,24(6)：431-434.
[19]Brandes RP, Janiszewski M. Direct detection of reactive oxygen species ex vivo [J]. Kidney Int.2005,67(5):1662.
[20]Pertynska MP, Tehorzewski H. Evaluation of the hormonal replaee therapy (HRT) effect on generation of reactive oxygen intermediates (ROI) by neutrophil in peripheral blood of menopausal women [J]. Ginekol Pol. 2000,71(2):55-62.
[21]万雷,刘庆思.绝经后骨质疏松症与活性氧的关系及中药骨康的抗氧化作用研究[D].广州中医药大学,2011：17-35.
[1]周俪姗,潘明政.北京协和医院住院2型糖尿病病人临床资料分析[D].北京中医药大学,2009：27.
[2]Yang WY, Lu JM, Weng JP, et al. Prevalence of diabetes among men and women in China [J]. N Engl J Med.2010,362(12):1090-1101.
[3]张蕙芬,迟家敏,王瑞萍.实用糖尿病学[M].北京：人民卫生出版社,1992：22-24.
[4]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21(2):296-309.
[5]胡善联,刘国恩,许樟荣等.我国糖尿病流行病学和疾病经济负担研究现状[J].中国卫生经济,2008,27(8)：5-8.
[6]廖二元,莫朝晖.内分泌学(第2版)[M].北京：人民卫生出版社,2007：1448-1449.
[7]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[8]张义德,周巧玲,刘志红.2型糖尿病肾病患者心脏结构、BMI与其临床表现及肾脏病理相关性研究[D].中南大学,2009：1-2.
[9]纪立农,陆菊明.预防血管事件,规范阿司匹林应用[J].中国医学论坛报,2011,37(6)：C9.
[10]许樟荣.速效胰岛素类似物应用于基础-餐时方案[J].中国医学论坛报,2011,37(2)：C9.
[11]杨文英.糖尿病领域年度事件之我见[J].中国医学论坛报,2011,37(1)：C4.
[12]冷三华,陆付耳.小檗碱治疗2型糖尿病临床和实验研究进展[J].中国中 西医结合杂志,2002,22(10)：794-795.
[13]孙连庆,梁晓春.中药降血糖机制实验研究进展[J].中华中医药杂志,2007,22(11)：789-791.
[14]王芬,何华亮,刘铜华.抗糖尿病中药活性成分及其作用机制的研究进展[J].时珍国医国药,2008,19(2)：766-767.
[15]兰卫,高晓黎,毛新民.胡芦巴药理作用的研究进展[J].西北药学杂志,2008,23(5)：335-337.
[16]Manisha M, Priyanjali D, Jayant L, et al. Indian Herbs and Herbal Drugs Used for the Treatment of Diabetes [J]. J Clin Biochem Nutr.2007,40(3):163-173.
[17]史江华,李多伟,逢敏杰等.胡芦巴研究新进展[J].西北药学杂志,2007,22(3)：153-155.
[18]Srinivasan K. Fenugreek (Trigonella foenum-graecum):A Review of Health Beneficial Physiological Effects [J]. Food Rev Int.2006,22(2):203-224.
[19]李琳琳,张月明,王雪飞等.胡芦巴粗提物对血糖和血脂作用的实验研究[J].新疆医科大学学报,2005,28(2)：98-101.
[20]孙晓风,李琳琳,毛新民.胡芦巴总皂苷对血脂紊乱模型大鼠生化指标的影响[J].新疆医科大学学报,2005,28(2)：101-103.
[21]Vats V, Grover J, Rathi S. Evaluation of antihyperglycemic and hypoglycemic effect of trigonella foenum-graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabeticrats [J]. J Ethnopharmacol.2002,79(1):95-100.
[22]Lu FR, Shen L, Qin Y, et al. Clinical observation on Trigonella foenum-graecum L.total saponins in combination with sulphanylureas in the treatment of type 2 diabetes mellitus [J]. Chin J Integr Med.2008,14(1):56-60.
[23]卢芙蓉,秦铀,沈霖等.胡芦巴总皂苷对饮食诱导肥胖大鼠糖脂代谢及胰岛素抵抗的影响[J].中国中医药信息杂志,2010,17(9)：34-36.
[24]Sharma RD. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects [J]. Nutr Res.1986,6(12):1353-1360.
[25]Fairchild RM, Ellis PR, Byrne AJ, et al. A new breakfast cereal containing guar gum reduces postprandial plasma glucose and insulin concentrations in normal-weight human subjects [J]. Br J Nutr.1996,76(1):63-73.
[26]Pick ME. Oat bran concentrate bread products improve long-term control of diabetes:a pilot study [J]. J Am Diet Assoc.1996,96(12):1254.
[27]Jenkins DJ. Effect of guar crispbread with cereal products and leguminous seeds on blood glucose concentrations of diabetics [J]. Br Med J. 1980,281(6250):1248-1252.
[28]Landin K, Holm G, Tengborn L, et al. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men [J]. Am J Clin Nutr.1992,56(6):1061-1065.
[29]Anchalee S, Catherine JF, Alan BRT, et al. The modifying effects of galactomannan from canadian-grown fenugreek (Trigonella foenum-graecum L.) on the glycemic and lipidemic status in rats [J]. J Clin Biochem Nutr. 2008,43(3):167-174.
[30]Broca C, Breil V, Cruciani-Guglielmacci C, et al. Insulinotropic agent ID-1101(4-hydroxyisoleucine)activates insulin signaling in rat [J]. Am J Physiol Endocrinol Metab.2004,287(3):E463-E471.
[31]Jette L, Harvey L, Eugeni K, et al.4-Hydroxyisoleucine:a plant-derived treatment for metabolic syndrome [J]. Curr Opin Investig Drugs. 2009,10(4):353.
[32]Claude C, Charles M, Alain W. Preparation of diastereoisomers of 4-hydroxyisoleucine:WO,2006117696 [P].2006-02-17. (CA 2006,145:471854).
[33]Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus [J]. J Diabet Complications.2001,15(4):203-210.
[34]Naziroglu M, Cay M. Protective role of intraperitoneally administered vitamin E and selenium on the oxidative defense mechanisms in rats with diabetes induced by streptozotocin [J]. Biol Trace Elem Res.2001,79(2):475-488.
[35]Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats [J]. Phytother Res. 1999,13(3):197-201.
[36]Anuradha CV, Ravikumar P. Restoration of tissue antioxidants by fenugreek seeds (Trigonella foenum graecum) in alloxan-diabetic rats [J]. Indian J Physiol Pharmacol.2001,45(4):408-420.
[37]张奠之,张瑜,李琳琳等.胡芦巴总皂苷对大鼠酒精性脂肪肝的治疗作用[J].中华肝脏病杂志,2006,14(11)：854-856.
[38]Devasena T, Menon VP. Enhancement of circulatory antioxidants by fenugreek during 1,2-dimethylhydrazine-induced rat colon carcinogenesis [J]. J Biochem Mol Biol Biophys.2002,6(4):289-292.
[39]Dixit PP, Ghaskadbi SS, Hari M, et al. Antioxidant properties of germinated fenugreek seeds [J]. Phytother Res.2005,19(11):977-983.
[40]Sangeetha R. Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim [J]. Indian J Pharm Sci.2010,72(1):116-118.
[41]Mohammad RVM, Mehrdad R, Tourandokht B. Mechanisms responsible for the vascular effect of aqueous Trigonella foenum-graecum leaf extract in diabetic rats [J]. Indian J Pharmacol.2008,40(2):59-63.
[42]Uma NT, Deepak C. The plant extracts of Momordica charantia and Trigonella foenum graecum have antioxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus [J]. Oxid Med Cell Longev. 2009,2(5):290-296.
[43]李琳琳,冉新建,毛新民等.胡芦巴总皂苷对脑缺血保护作用[J].中国药 理学通报,2001,7(1)：92-94.
[44]卢芙蓉,秦铀,沈霖等.胡芦巴总皂苷对链脲佐霉素诱导的糖尿病大鼠血小板活化的调节作用[J].中国医院药学杂志,2010,30(5)：369-372.
[45]Thakran S, Siddiqui MR, Baquer NZ. Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats [J]. Mol Cell Biochem.2004,266(1-2):151-159.
[46]卢芙蓉,秦铀,沈霖等.胡芦巴提取物对肾病综合征大鼠肾损伤的保护作用[J].中西医结合研究,2009,1(6)：281-284.
[47]阮耀,黄川锋.胡芦巴对糖尿病大鼠肾脏保护作用的实验研究[J].中国中医药科技,2008,15(6)：432-433.
[48]何颖,肖常青.氧化型低密度脂蛋白与糖尿病肾病关系的研究进展[J].医学综述,2010,16(4)：620-622.
[49]常明,刘书馨,杨溟等.高糖对系膜细胞诱生型一氧化氮合酶表达及细胞外基质合成的影响[J].中国中西医结合肾病杂志,2005,6(4)：204-208.
[50]Simonson MS. Phenotypic transitions and fibrosis in diabetic nephropathy [J]. Kidney Int.2007,71 (9):846-854.
[51]Strutz F, Zeisberg M. Renal fibroblasts andmyofibroblasts in chronic kidney disease [J]. J Am Soc Nephrol.2006,17(11):2992-2998.
[52]徐西振,涂玲,郑常龙等.人组织型激肽释放酶基因对大鼠糖尿病肾病的影响及其机制[J].中国中西医结合肾病杂志,2008,9(6)：490-493.
[53]Ziyadeh FN. Mediator ofdiabetes renal diseases:the case for TGF-β asmajormediator [J]. J Am Soc Nephrol.2004,15(1):S55-S57.
[54]Han SY, Jee YH, Han KH, et al. An imbalance between matrix metalloproteinase-2 and tissue inhibitorofinatrixmetalloproteinase-2 contributes to the developmentofearly diabetic nephropathy [J]. Nephrol Dial Transplant.2006,21(9):2406-2416.
[55]D'Agord SB, Lacchini S, Bertoluci MC, et al. Increased renal GLUT1abundance and urinary TGF betal in streptozotocin induced diabetic rats:implications for the development of nephropathy complicating diabetes [J]. Horm Metab Res.2001,33(11):664-669.
[56]Liu ZH, Li LS. Glucose transporanters implication for diabetic nephropathy [J]. CNDT.1998,7(5):205-209.
[57]程文荣,刘丽秋.来氟米特对糖尿病大鼠葡糖糖转运蛋白-1mRNA表达及细胞外基质的影响[J].中国中西医结合肾病杂志,2008,9(2)：121-125.
[58]李英,段惠军,张丽红.缬沙坦对高糖环境下系膜细胞GLUTl表达的影响[J].中国中西医结合肾病杂志,2008,9(3)：240-241.
[59]陈雪功,周雪梅,张琼玉等.冬梅饮对早期糖尿病肾病大鼠肾组织非酶糖基化终产物的影响[J].中国实验方剂学杂志,2007,13(1)：41-43.
[60]费洪华,肖正大,高薇.虎杖免煎冲剂对糖尿病大鼠肾脏RAGE及VEGF表达的影响[J].山东大学学报(医学版),2008,46(1)：43-47.
[61]Zingg JM, Ricciarelli R, Azzi A. Scavenger receptors and modified lipoproteins:fatal attractions [J]. IUBMB Life.2000,49(5):397-403.
[62]李萍,盛志叶,马小峰等.LOX-1在ox-LDL诱导肾小球系膜细胞表达TGF-β1中的作用[J].沈阳部队医药,2006,19(3)：160-164.
[63]王远程,叶志斌,周钦等.丙丁酚抑制氧化型低密度脂蛋白诱导系膜细胞转化生长因子β1表达[J].复旦学报(医学版),2005,32(2)：151-154.
[2]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21 (2):296-309.
[3]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[4]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91 (2):261-270.
[5]Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury:activation of polyol pathway and oxidative stress responsive signaling cascades [J]. Chem Biol Interact. 2009,181 (3):297-308.
[6]Manna P, Sinha M, Sil PC. Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction [J]. Amino Acids. 2009,36(3):417-428.
[7]Lu FR, Shen L, Qin Y, et al. Clinical observation on Trigonella foenum-graecum L. total saponins in combination with sulphanylureas in the treatment of type 2 diabetes mellitus [J]. Chin J Integr Med.2008,14(1):56-60.
[8]Anchalee S, Catherine JF, Alan BRT, et al. The modifying effects of galactomannan from canadian-grown fenugreek (Trigonella foenum-graecum L.) on the glycemic and lipidemic status in rats [J]. J Clin Biochem Nutr. 2008,43(3):167-174.
[9]Broca C, Breil V, Cruciani-Guglielmacci C, et al. Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat [J]. Am J Physiol Endocrinol Metab.2004,287(3):E463-E471.
[10]Jette L, Harvey L, Eugeni K, et al.4-Hydroxyisoleucine:a plant-derived treatment for metabolic syndrome [J]. Curr Opin Investig Drugs. 2009,10(4):353.
[11]Bapat K, Chintalwar GJ, Pandey U, et al. Prepration and in vitro evaluation of radioiodinated bakuchiol as an antitumour agent [J]. Appl Radiat Isot. 2005,62(3):389-393.
[12]Khatune NA, Islam ME, Haque ME, et al. Antibacterial compounds from seeds of Psoralea corylifolia L [J]. Fitoterapia.2004,75(2):228-230.
[13]Xiong Z, Wang D, Xu Y, et al. Osteoblastic differentiation bioassay and its application to investigating the activity of fractions and compounds from Psoralea corylifolia L [J]. Pharmazie.2003,58(12):925-928.
[14]Uma NT, Deepak C. The plant extracts of Momordica charantia and Trigonella foenum graecum have antioxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus [J]. Oxid Med Cell Longev. 2009,2(5):290-296.
[15]Sangeetha R. Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim [J]. Indian J Pharm Sci.2010,72(1):116-118.
[16]Soon YT, Jan G, Kim PW, et al. Psoralea corylifolia L. Inhibits Mitochondrial Complex I and Proteasome Activities in SH-SY5Y Cells [J]. Ann N Y Acad Sci.2007,1100(1):486-496.
[17]Sumira J, Talat P, Siddiqi TO, et al. Anti-oxidant modulation in response to gamma radiation induced oxidative stress in developing seedlings of Psoralea corylifolia L[J]. J Environ Radioact.2012,113(1):142-149.
[18]Thakran S, Siddiqui MR, Baquer NZ. Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats [J]. Mol Cell Biochem.2004,266(1-2):151-159.
[19]Kim YC, Oh H, Kim BS, et al. In vitro Protein Tyrosine Phosphatase IB Inhibitory Phenols from the Seeds of Psoralea corylifolia [J]. Planta Med. 2005,71(1):87-89.
[20]Helena P, Charles WL, Shyamali B, et al. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures [J]. J Cereb Blood Flow Metab.2012,32(6):1024-1034.
[21]Hari H, Toyoshi I, Yasutaka M, et al. GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases [J]. Metabolism.2012,61(10):1422-1434.
[22]Osamu K, Kazuhide U, Hisayo K, et al. Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells [J]. Clin Exp Nephrol.2009,13(1):15-24.
[23]Jesys AC, Elizabeth AZ, Robert C, et al. Uncoupling protein-2 expression and effects on mitochondrial membrane potential and oxidant stress in heart tissue [J]. Transl Res.2012,159(5):383-390.
[24]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91(2):261-270.
[25]Ralf PB, Jorg K. Vascular NADPH oxidases:molecular mechanisms of activation [J]. Cardiovasc Res.2005,65(1):16-27.
[26]Seiya S, Harukiyo K, Minoru T, et al. Halofuginone prevents extracellular matrix deposition in diabetic nephropathy [J]. Biochem Biophys Res Commun. 2009,379(2):411-416.
[27]Lin CC, Lin LT, Yen MH, et al. Renal Protective Effect of Xiao-Chai-Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice [J]. Evid Based Complement Alternat Med.2012,2012(1):984024.
[28]Larissa P, Mayara SG, Carolina BAR, et al. The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat [J]. Eur J Pharmacol.2012,678(1-3):15-25.
[29]Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes [J]. Diabetes.2008,57(6):1446-1454.
[30]Toba H, Sawai N, Morishita M, et al. Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat [J]. Eur J Pharmacol. 2009,612(1-3):106-114.
[1]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21(2):296-309.
[2]胡善联,刘国恩,许樟荣等.我国糖尿病流行病学和疾病经济负担研究现状[J].中国卫生经济,2008,227(8)：5-8.
[3]Yang WY, Lu JM, Weng JP, et al. Prevalence of diabetes among men and women in China [J]. N Engl J Med.2012,362(12):1090-1101.
[4]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[5]廖二元,莫朝晖.内分泌学(第2版)[M].北京：人民卫生出版社,2007：1448-1449.
[6]Winiarska K, Szymanski K, Gorniak P, et al. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits [J]. Biochimie. 2009,91(2):261-270.
[7]Manna P, Sinha M, Sil PC. Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury:activation of polyol pathway and oxidative stress responsive signaling cascades [J]. Chem Biol Interact. 2009,181(3):297-308.
[8]Manna P, Sinha M, Sil PC. Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction [J]. Amino Acids. 2009,36(3):417-428.
[9]宋根萍.灰兜巴有效成分的提取方法：中国,CN101380339A[P]. 2009-03-11.
[10]刘艳,周慧,滕利荣.灰兜巴多糖的提取及其降血糖活性的研究[D].吉林大学,2009：4.
[11]赵劲航,田淑琴.中药复方灰兜巴对糖尿病治疗作用研究[J].西南民族大学学报·自然科学版,2008,34(6)：1186-1188.
[12]赵敏,宋静静,王贞佐等.复方灰兜巴预防及治疗糖尿病的实验研究[J].食品及药物,2011,13(7)：254-257.
[13]彭亮,李知敏.灰兜巴抗糖尿病作用的实验研究[J].时珍国医国药,2010,21(12)：3060-3061.
[14]彭亮,李知敏,徐玲.灰兜巴提取物体外清除自由基活性的研究[J].安徽农业科学,2010,38(14)：7343-7344,7347.
[15]黄琳,陆付耳,杨小玉等.黄连解毒汤对胰岛素抵抗大鼠肝脏线粒体氧化应激的影响[J].中国中西医结合杂志,2008,28(8)：725-728.
[16]Ralf PB, Jorg K. Vascular NADPH oxidases:molecular mechanisms of activation [J]. Cardiovasc Res.2005,65(1):16-27.
[17]Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes [J]. Diabetes.2008,57(6):1446-1454.
[18]Toba H, Sawai N, Morishita M, et al. Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat [J]. Eur J Pharmacol. 2009,612(1-3):106-114.
[1]Cole ZA, Dennison EM, Cooper C. Osteoporosis epidemiology update [J]. Curr Rheumatol Rep.2008,10(2):92-96.
[2]薛延.骨质疏松症的流行病学概况[J].新医学,2007,38(1)：7-8.
[3]Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States,2005-2025 [J]. J Bone Miner Res.2007,22(3):465-475.
[4]章振林.骨质疏松流行病学现状[J].中华医学杂志,2009,89(42)：2953-2955.
[5]Lydick E, Cook K, Turpin J, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density [J]. Am J Manag Care.1998,4(l):37-48.
[6]Kanis J. Assessment of osteoporosis at the primary health care level [R]. World Health Organization Collaborating Centre For Metabolic Bone Diseases. University Of Sheffield, UK:2008.
[7]Ben SW, Chevallier T, Zegels B, et al. Development and assessment of the Osteoporosis Index of Risk (OSIRIS) to facilitate selection of women for bone densitometry [J]. Gynecol Endocrinol.2002,16(3):245-250.
[8]张菊英,吴涛,杨定焯等.中国大陆地区妇女骨质疏松筛选工具探讨[J].中国修复重建外科杂志,2007,21(1)：86-89.
[9]Cadarette SM, Jaglal SB, Kreiger N, et al. Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry [J]. CMAJ.2000,162(9):1289-1294.
[10]Vikram ST, Timothy C, Isaac M. Exploiting the antioxidant potential of a common vitamin:Could vitamin C prevent postmenopausal osteoporosis [J]? J Obstet Gynaecol Res.2012,38(1):253-257.
[11]Maryam SH, Paul NC, Angela MC. Effects of vitamin E on bone turnover markers among US postmenopausal women [J]. J Bone Miner Res. 2012,27(6):1368-1380.
[12]Serap Y, Ozgun S, Ulku C, et al. Strontium ranelate treatment improves oxidative damage in osteoporotic rat model [J]. Pharmacol Rep. 2012,64(2):396-402.
[13]Zhang YB, Zhong ZM, Hou G, et al. Involvement of Oxidative Stress in Age-Related Bone Loss [J]. J Surg Res.2011,169(1):e37-e42.
[14]WHO:Guidelines for Preclinical Evaluation And Clinical Trials In Osteoporosis [R]. Geneva:1998.
[15]田峰,谢雁鸣.绝经后骨质疏松症危险因素、预测模型和筛检工具研究[J].中国骨质疏松杂志,2011,17(2)：166-171.
[16]Rossouw JE, Anderson GL, Prentice RL, et al. Risk and benefit of estrogen plus progestin in healthy postmenopausal women:principal results from the women's health initiative randomized controlled trial [J]. JAMA. 2002,288(3):321.
[17]Lin JT, Lane JM. Osteoporosis:A review [J]. Clin Orthop Relat Res. 2004,425(1):126.
[18]单鹏飞,伍贤平,廖二元等.女性骨代谢转换生化指标和骨密度随龄变化及其相互关系[J].中华老年医学杂志,2005,24(6)：431-434.
[19]Brandes RP, Janiszewski M. Direct detection of reactive oxygen species ex vivo [J]. Kidney Int.2005,67(5):1662.
[20]Pertynska MP, Tehorzewski H. Evaluation of the hormonal replaee therapy (HRT) effect on generation of reactive oxygen intermediates (ROI) by neutrophil in peripheral blood of menopausal women [J]. Ginekol Pol. 2000,71(2):55-62.
[21]万雷,刘庆思.绝经后骨质疏松症与活性氧的关系及中药骨康的抗氧化作用研究[D].广州中医药大学,2011：17-35.
[1]周俪姗,潘明政.北京协和医院住院2型糖尿病病人临床资料分析[D].北京中医药大学,2009：27.
[2]Yang WY, Lu JM, Weng JP, et al. Prevalence of diabetes among men and women in China [J]. N Engl J Med.2010,362(12):1090-1101.
[3]张蕙芬,迟家敏,王瑞萍.实用糖尿病学[M].北京：人民卫生出版社,1992：22-24.
[4]American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997 [J]. Diabetes Care.1998,21(2):296-309.
[5]胡善联,刘国恩,许樟荣等.我国糖尿病流行病学和疾病经济负担研究现状[J].中国卫生经济,2008,27(8)：5-8.
[6]廖二元,莫朝晖.内分泌学(第2版)[M].北京：人民卫生出版社,2007：1448-1449.
[7]Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population:do we know the cause [J]? Kidney Int.2005,67(5):1684-1691.
[8]张义德,周巧玲,刘志红.2型糖尿病肾病患者心脏结构、BMI与其临床表现及肾脏病理相关性研究[D].中南大学,2009：1-2.
[9]纪立农,陆菊明.预防血管事件,规范阿司匹林应用[J].中国医学论坛报,2011,37(6)：C9.
[10]许樟荣.速效胰岛素类似物应用于基础-餐时方案[J].中国医学论坛报,2011,37(2)：C9.
[11]杨文英.糖尿病领域年度事件之我见[J].中国医学论坛报,2011,37(1)：C4.
[12]冷三华,陆付耳.小檗碱治疗2型糖尿病临床和实验研究进展[J].中国中 西医结合杂志,2002,22(10)：794-795.
[13]孙连庆,梁晓春.中药降血糖机制实验研究进展[J].中华中医药杂志,2007,22(11)：789-791.
[14]王芬,何华亮,刘铜华.抗糖尿病中药活性成分及其作用机制的研究进展[J].时珍国医国药,2008,19(2)：766-767.
[15]兰卫,高晓黎,毛新民.胡芦巴药理作用的研究进展[J].西北药学杂志,2008,23(5)：335-337.
[16]Manisha M, Priyanjali D, Jayant L, et al. Indian Herbs and Herbal Drugs Used for the Treatment of Diabetes [J]. J Clin Biochem Nutr.2007,40(3):163-173.
[17]史江华,李多伟,逢敏杰等.胡芦巴研究新进展[J].西北药学杂志,2007,22(3)：153-155.
[18]Srinivasan K. Fenugreek (Trigonella foenum-graecum):A Review of Health Beneficial Physiological Effects [J]. Food Rev Int.2006,22(2):203-224.
[19]李琳琳,张月明,王雪飞等.胡芦巴粗提物对血糖和血脂作用的实验研究[J].新疆医科大学学报,2005,28(2)：98-101.
[20]孙晓风,李琳琳,毛新民.胡芦巴总皂苷对血脂紊乱模型大鼠生化指标的影响[J].新疆医科大学学报,2005,28(2)：101-103.
[21]Vats V, Grover J, Rathi S. Evaluation of antihyperglycemic and hypoglycemic effect of trigonella foenum-graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabeticrats [J]. J Ethnopharmacol.2002,79(1):95-100.
[22]Lu FR, Shen L, Qin Y, et al. Clinical observation on Trigonella foenum-graecum L.total saponins in combination with sulphanylureas in the treatment of type 2 diabetes mellitus [J]. Chin J Integr Med.2008,14(1):56-60.
[23]卢芙蓉,秦铀,沈霖等.胡芦巴总皂苷对饮食诱导肥胖大鼠糖脂代谢及胰岛素抵抗的影响[J].中国中医药信息杂志,2010,17(9)：34-36.
[24]Sharma RD. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects [J]. Nutr Res.1986,6(12):1353-1360.
[25]Fairchild RM, Ellis PR, Byrne AJ, et al. A new breakfast cereal containing guar gum reduces postprandial plasma glucose and insulin concentrations in normal-weight human subjects [J]. Br J Nutr.1996,76(1):63-73.
[26]Pick ME. Oat bran concentrate bread products improve long-term control of diabetes:a pilot study [J]. J Am Diet Assoc.1996,96(12):1254.
[27]Jenkins DJ. Effect of guar crispbread with cereal products and leguminous seeds on blood glucose concentrations of diabetics [J]. Br Med J. 1980,281(6250):1248-1252.
[28]Landin K, Holm G, Tengborn L, et al. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men [J]. Am J Clin Nutr.1992,56(6):1061-1065.
[29]Anchalee S, Catherine JF, Alan BRT, et al. The modifying effects of galactomannan from canadian-grown fenugreek (Trigonella foenum-graecum L.) on the glycemic and lipidemic status in rats [J]. J Clin Biochem Nutr. 2008,43(3):167-174.
[30]Broca C, Breil V, Cruciani-Guglielmacci C, et al. Insulinotropic agent ID-1101(4-hydroxyisoleucine)activates insulin signaling in rat [J]. Am J Physiol Endocrinol Metab.2004,287(3):E463-E471.
[31]Jette L, Harvey L, Eugeni K, et al.4-Hydroxyisoleucine:a plant-derived treatment for metabolic syndrome [J]. Curr Opin Investig Drugs. 2009,10(4):353.
[32]Claude C, Charles M, Alain W. Preparation of diastereoisomers of 4-hydroxyisoleucine:WO,2006117696 [P].2006-02-17. (CA 2006,145:471854).
[33]Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus [J]. J Diabet Complications.2001,15(4):203-210.
[34]Naziroglu M, Cay M. Protective role of intraperitoneally administered vitamin E and selenium on the oxidative defense mechanisms in rats with diabetes induced by streptozotocin [J]. Biol Trace Elem Res.2001,79(2):475-488.
[35]Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats [J]. Phytother Res. 1999,13(3):197-201.
[36]Anuradha CV, Ravikumar P. Restoration of tissue antioxidants by fenugreek seeds (Trigonella foenum graecum) in alloxan-diabetic rats [J]. Indian J Physiol Pharmacol.2001,45(4):408-420.
[37]张奠之,张瑜,李琳琳等.胡芦巴总皂苷对大鼠酒精性脂肪肝的治疗作用[J].中华肝脏病杂志,2006,14(11)：854-856.
[38]Devasena T, Menon VP. Enhancement of circulatory antioxidants by fenugreek during 1,2-dimethylhydrazine-induced rat colon carcinogenesis [J]. J Biochem Mol Biol Biophys.2002,6(4):289-292.
[39]Dixit PP, Ghaskadbi SS, Hari M, et al. Antioxidant properties of germinated fenugreek seeds [J]. Phytother Res.2005,19(11):977-983.
[40]Sangeetha R. Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim [J]. Indian J Pharm Sci.2010,72(1):116-118.
[41]Mohammad RVM, Mehrdad R, Tourandokht B. Mechanisms responsible for the vascular effect of aqueous Trigonella foenum-graecum leaf extract in diabetic rats [J]. Indian J Pharmacol.2008,40(2):59-63.
[42]Uma NT, Deepak C. The plant extracts of Momordica charantia and Trigonella foenum graecum have antioxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus [J]. Oxid Med Cell Longev. 2009,2(5):290-296.
[43]李琳琳,冉新建,毛新民等.胡芦巴总皂苷对脑缺血保护作用[J].中国药 理学通报,2001,7(1)：92-94.
[44]卢芙蓉,秦铀,沈霖等.胡芦巴总皂苷对链脲佐霉素诱导的糖尿病大鼠血小板活化的调节作用[J].中国医院药学杂志,2010,30(5)：369-372.
[45]Thakran S, Siddiqui MR, Baquer NZ. Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats [J]. Mol Cell Biochem.2004,266(1-2):151-159.
[46]卢芙蓉,秦铀,沈霖等.胡芦巴提取物对肾病综合征大鼠肾损伤的保护作用[J].中西医结合研究,2009,1(6)：281-284.
[47]阮耀,黄川锋.胡芦巴对糖尿病大鼠肾脏保护作用的实验研究[J].中国中医药科技,2008,15(6)：432-433.
[48]何颖,肖常青.氧化型低密度脂蛋白与糖尿病肾病关系的研究进展[J].医学综述,2010,16(4)：620-622.
[49]常明,刘书馨,杨溟等.高糖对系膜细胞诱生型一氧化氮合酶表达及细胞外基质合成的影响[J].中国中西医结合肾病杂志,2005,6(4)：204-208.
[50]Simonson MS. Phenotypic transitions and fibrosis in diabetic nephropathy [J]. Kidney Int.2007,71 (9):846-854.
[51]Strutz F, Zeisberg M. Renal fibroblasts andmyofibroblasts in chronic kidney disease [J]. J Am Soc Nephrol.2006,17(11):2992-2998.
[52]徐西振,涂玲,郑常龙等.人组织型激肽释放酶基因对大鼠糖尿病肾病的影响及其机制[J].中国中西医结合肾病杂志,2008,9(6)：490-493.
[53]Ziyadeh FN. Mediator ofdiabetes renal diseases:the case for TGF-β asmajormediator [J]. J Am Soc Nephrol.2004,15(1):S55-S57.
[54]Han SY, Jee YH, Han KH, et al. An imbalance between matrix metalloproteinase-2 and tissue inhibitorofinatrixmetalloproteinase-2 contributes to the developmentofearly diabetic nephropathy [J]. Nephrol Dial Transplant.2006,21(9):2406-2416.
[55]D'Agord SB, Lacchini S, Bertoluci MC, et al. Increased renal GLUT1abundance and urinary TGF betal in streptozotocin induced diabetic rats:implications for the development of nephropathy complicating diabetes [J]. Horm Metab Res.2001,33(11):664-669.
[56]Liu ZH, Li LS. Glucose transporanters implication for diabetic nephropathy [J]. CNDT.1998,7(5):205-209.
[57]程文荣,刘丽秋.来氟米特对糖尿病大鼠葡糖糖转运蛋白-1mRNA表达及细胞外基质的影响[J].中国中西医结合肾病杂志,2008,9(2)：121-125.
[58]李英,段惠军,张丽红.缬沙坦对高糖环境下系膜细胞GLUTl表达的影响[J].中国中西医结合肾病杂志,2008,9(3)：240-241.
[59]陈雪功,周雪梅,张琼玉等.冬梅饮对早期糖尿病肾病大鼠肾组织非酶糖基化终产物的影响[J].中国实验方剂学杂志,2007,13(1)：41-43.
[60]费洪华,肖正大,高薇.虎杖免煎冲剂对糖尿病大鼠肾脏RAGE及VEGF表达的影响[J].山东大学学报(医学版),2008,46(1)：43-47.
[61]Zingg JM, Ricciarelli R, Azzi A. Scavenger receptors and modified lipoproteins:fatal attractions [J]. IUBMB Life.2000,49(5):397-403.
[62]李萍,盛志叶,马小峰等.LOX-1在ox-LDL诱导肾小球系膜细胞表达TGF-β1中的作用[J].沈阳部队医药,2006,19(3)：160-164.
[63]王远程,叶志斌,周钦等.丙丁酚抑制氧化型低密度脂蛋白诱导系膜细胞转化生长因子β1表达[J].复旦学报(医学版),2005,32(2)：151-154.