人参皂苷CK对2型糖尿病大鼠肾脏的保护作用
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摘要
目的探讨人参皂苷CK对糖尿病大鼠肾脏的保护机制.方法选择雄性Wistar大鼠,以高脂饲料喂养,并给予小剂量链尿佐菌素(STZ),诱导产生2型糖尿病大鼠模型(T2DM).将T2DM大鼠随机分为模型组、CK高剂量组(10.5 mg/kg)和CK低剂量组(5.25 mg/kg),并分别给予灌胃,正常对照组喂普通饲料,模型组及给药组喂高脂饲料.药物干预7周后,采集大鼠血清与肾组织,测定血糖、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、尿素氮(BUN)、尿酸(UA)、血肌酐(Scr)、丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-PX)的活力; HE染色观察肾组织病理变化; Western blot法检测肾组织中TGF-β1蛋白的表达,将结果进行统计学分析.结果与正常对照组比较,模型组大鼠空腹血糖、TC、TG、LDL-C、血清BUN、UA、Scr、MDA含量、TGF-β1蛋白表达量升高,HDL-C、GSH含量降低,SOD,GSH-PX活力降低(P<0.05);给药后,CK高、低剂量组与模型组比较,空腹血糖、TC、TG、LDL-C、BUN、UA、Scr、MDA含量降低,TGF-β1蛋白表达量降低,HDL-C、GSH含量升高,SOD、GSH-PX活力升高,(P<0.05).结论人参皂苷CK能通过增强大鼠肾组织的抗氧化能力,增强肾小球滤过功能,促进肾组织结构恢复,抑制肾组织中TGF-β1的表达,从而降低血糖,调节血脂,减少TGF-β1对肾组织结构的损伤.
Objective To investigate the protective mechanisms of ginsenoside CK on the kidney of diabetic rats.Method Male Wistar rats were fed with high-fat diet,and given low-dose streptozotocin(STZ) intraperitoneal injection to induce a rat model of type 2 diabetes. T2 DM rats were randomly divided into model group,CK advanced group(10.5 mg/kg) and CK low dose group(5.25 mg/kg) and by gavage.The normal control group was fed ordinary diet,the model group and the drug group were fed high-fatdiet. After 7 weeks of drug intervention,rat serum and kidney tissue were collected,and blood sugar,Triglyceride(TG),Total cholesterol(TC),High-density lipoprotein(HDL-C),Low density lipoprotein(LDL-C),Blood uria nitrogen(BUN),Uric acid(UA),Serum creatinine(Scr),Malondialdehyde(MDA) and Glutathione(GSH) and Superoxide dismutase(SOD),Glutathione peroxidase(GSH-PX) activity were determined.The pathological changes of renal tissues were observed by HE staining.The expression of TGF-β1 protein in renal tissues was detected by Western blot.The results were statistically analyzed.Results Compared with the normal control group,the levels of rats' fasting blood-glucose in model group,TC,TG,LDL-C,BUN,UA,Scr,MDA,TGF-β1 protein expression were increased,the levels of HDL-C,GSH content were decreased,the vitality of SOD,GSH-PX were decreased(P<0.05). Conclusion Ginsenoside CK may reduce blood sugar,regulate blood lipids,enhance the antioxidant capacity of rat kidney tissue,enhance glomerular filtration function,promote renal tissue structure recovery,inhibit the expression of TGF-β1 in renal tissue,thereby reducing TGF-β1 damage to kidney tissue structure.
Objective To investigate the protective mechanisms of ginsenoside CK on the kidney of diabetic rats.Method Male Wistar rats were fed with high-fat diet,and given low-dose streptozotocin(STZ) intraperitoneal injection to induce a rat model of type 2 diabetes. T2 DM rats were randomly divided into model group,CK advanced group(10.5 mg/kg) and CK low dose group(5.25 mg/kg) and by gavage.The normal control group was fed ordinary diet,the model group and the drug group were fed high-fatdiet. After 7 weeks of drug intervention,rat serum and kidney tissue were collected,and blood sugar,Triglyceride(TG),Total cholesterol(TC),High-density lipoprotein(HDL-C),Low density lipoprotein(LDL-C),Blood uria nitrogen(BUN),Uric acid(UA),Serum creatinine(Scr),Malondialdehyde(MDA) and Glutathione(GSH) and Superoxide dismutase(SOD),Glutathione peroxidase(GSH-PX) activity were determined.The pathological changes of renal tissues were observed by HE staining.The expression of TGF-β1 protein in renal tissues was detected by Western blot.The results were statistically analyzed.Results Compared with the normal control group,the levels of rats' fasting blood-glucose in model group,TC,TG,LDL-C,BUN,UA,Scr,MDA,TGF-β1 protein expression were increased,the levels of HDL-C,GSH content were decreased,the vitality of SOD,GSH-PX were decreased(P<0.05). Conclusion Ginsenoside CK may reduce blood sugar,regulate blood lipids,enhance the antioxidant capacity of rat kidney tissue,enhance glomerular filtration function,promote renal tissue structure recovery,inhibit the expression of TGF-β1 in renal tissue,thereby reducing TGF-β1 damage to kidney tissue structure.
引文
[1]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.
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[6]陈永欣,韦锦斌.链脲佐菌素诱导大鼠2型糖尿病并发症模型研究进展[J].中国比较医学杂志,2013,23(3):63-66.
[7]安丽萍.人参皂苷CK改善2型糖尿病大鼠骨骼肌胰岛素抵抗作用[A].中国药理学会补益药药理专业委员会.第三届中国药理学会补益药药理专业委员会学术研讨会论文集[C].中国药理学会补益药药理专业委员会,2013:2.
[8]韩鹏飞,李洪志,于晶,等.姜黄素及其类似物通过抑制炎症因子对糖尿病肾病小鼠的治疗作用[J].时珍国医国药,2017,28(1):77-81.
[9]牛洪琳.基质金属蛋白酶12表达对糖尿病肾病及高脂肾损伤的肾保护作用及其机制的研究[D].石家庄:河北医科大学,2016.
[10] Whiteside C,Katz A,Cho C,et al.Diabetic glomeru-lopathy following unilateral nephrectomy in the dog[J].Clin Invest Med,1990,13(5):279-286.
[11]徐叔云,卞如濂,陈修.药理实验方法学[M].3版.北京:人民卫生出版社,2002:1516-1522.
[12] Sugano M,Yamato H,Hayashi T,et al.High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephro-pathy:a new rat model of diabetic nephropathy[J]. Nutr Metab Cardiovasc Dis,2006,16(7):477-484.
[13]徐颖,周世文,汤建林,等.实验性糖尿病肾病大鼠模型建立及优化[J].第三军医大学学报,2006,28(22):2247-2249.
[14]倪红霞.高糖高脂饮食诱导的大鼠Ⅱ型糖尿病模型[J].北华大学学报(自然科学版),2006,7(5):440-442.
[15] Inoguchi T,Sonta T,Tsubouchi H,et al.Protein kinase C dependent increase in reactive oxygen species(ROS)production in vascular tissues of diabetes:role of vascular NADPH oxidase[J].J Am Soc Nephrol,2003,14:S227-S232.
[16] Dominguec J H,Tang N,Xu W,et al.Studies of renal inj-uryⅢ:Lipid-induced nephropathy in typeⅡdiabetes[J].Kidey Int,2002,3:196-198.
[17] Busch M,Franke S,Ruster C,et al.Advanced glycation end-products and the kidney[J].Eur J Clin Invest,2010,40:742-755.
[18]孔繁晟.甘蔗糖蜜中活性因子降血糖血脂作用及机理研究[D].广州:华南理工大学,2015.
[2]李娜,孙汇,王拓,等.糖尿病肾病发病机制研究进展[J].北华大学学报(自然科学版),2012,13(1):68-72.
[3] Durvasula R V,Shankland S J.Activation of a local rein angiotensin system in podocytes by glucose[J].Am J Physiol Renal Physiol,2008,294(4):830-839.
[4]刘媛媛.人参皂苷组合转化组分抗肿瘤活性的研究[D].扬州:扬州大学,2015.
[5]李相鹏,王鹏,李英霞.原人参二醇型皂苷活性代谢物Compound K药理活性的研究进展[J].中国药理学与毒理学杂志,2011,25(1):97-101.
[6]陈永欣,韦锦斌.链脲佐菌素诱导大鼠2型糖尿病并发症模型研究进展[J].中国比较医学杂志,2013,23(3):63-66.
[7]安丽萍.人参皂苷CK改善2型糖尿病大鼠骨骼肌胰岛素抵抗作用[A].中国药理学会补益药药理专业委员会.第三届中国药理学会补益药药理专业委员会学术研讨会论文集[C].中国药理学会补益药药理专业委员会,2013:2.
[8]韩鹏飞,李洪志,于晶,等.姜黄素及其类似物通过抑制炎症因子对糖尿病肾病小鼠的治疗作用[J].时珍国医国药,2017,28(1):77-81.
[9]牛洪琳.基质金属蛋白酶12表达对糖尿病肾病及高脂肾损伤的肾保护作用及其机制的研究[D].石家庄:河北医科大学,2016.
[10] Whiteside C,Katz A,Cho C,et al.Diabetic glomeru-lopathy following unilateral nephrectomy in the dog[J].Clin Invest Med,1990,13(5):279-286.
[11]徐叔云,卞如濂,陈修.药理实验方法学[M].3版.北京:人民卫生出版社,2002:1516-1522.
[12] Sugano M,Yamato H,Hayashi T,et al.High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephro-pathy:a new rat model of diabetic nephropathy[J]. Nutr Metab Cardiovasc Dis,2006,16(7):477-484.
[13]徐颖,周世文,汤建林,等.实验性糖尿病肾病大鼠模型建立及优化[J].第三军医大学学报,2006,28(22):2247-2249.
[14]倪红霞.高糖高脂饮食诱导的大鼠Ⅱ型糖尿病模型[J].北华大学学报(自然科学版),2006,7(5):440-442.
[15] Inoguchi T,Sonta T,Tsubouchi H,et al.Protein kinase C dependent increase in reactive oxygen species(ROS)production in vascular tissues of diabetes:role of vascular NADPH oxidase[J].J Am Soc Nephrol,2003,14:S227-S232.
[16] Dominguec J H,Tang N,Xu W,et al.Studies of renal inj-uryⅢ:Lipid-induced nephropathy in typeⅡdiabetes[J].Kidey Int,2002,3:196-198.
[17] Busch M,Franke S,Ruster C,et al.Advanced glycation end-products and the kidney[J].Eur J Clin Invest,2010,40:742-755.
[18]孔繁晟.甘蔗糖蜜中活性因子降血糖血脂作用及机理研究[D].广州:华南理工大学,2015.