胰岛素敏感性、胰岛素样生长因子结合蛋白-1与老年期痴呆中医证型关系的临床研究
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摘要
目的：探讨胰岛素敏感性(ISI)和血清胰岛素样生长因子结合蛋白－1(IGFBP-1)与老年期痴呆中医辨证分型的关系及临床意义。
方法：临床搜集2008年11月－2009年7月南京市鼓楼医院老年科门诊及住院病人,分为观察组和对照组。观察组为老年期痴呆患者,按中医分型标准,又分为2个亚组：脾肾两虚亚组和痰瘀兼气虚亚组。对照组为老年期非痴呆患者。运用ELISA法检测胰岛素样生长因子结合蛋白-1(IGFBP-1),放射免疫法检测空腹血清胰岛素(FINS),计算胰岛素敏感性指数(IAI),比较观察组各亚组与对照组间空腹血糖(FBG)、FINS、IAI、IGFBP-1、血脂、血压及简易智能精神状态检查量表(MMSE)评分等指标。
结果：1、观察组中的脾肾两虚亚组、痰瘀兼气虚亚组和对照组相比,FBG无统计学差异(P>0.05)。2、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,FINS升高,有显著统计学差异(P<0.01)；脾肾两虚亚组的FINS高于痰瘀兼气虚亚组,此两组之间存在显著统计学差异(P<0.01)。3、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,IAI下降,有统计学差异(P<0.01,P<0.05)；脾肾两虚亚组的IAI低于痰瘀兼气虚亚组,此两组间存在统计学差异(P<0.05)。4、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,IGFBP-1均升高,有显著统计学差异(P<0.01);脾肾两虚亚组的IGFBP-1高于痰瘀兼气虚亚组,此两组间存在统计学差异(P<0.05)。5、通过Pearson相关性分析可以看出,IGFBP-1与FBG、FINS、IAI有相关性,与FBG、FINS呈正相关,与IAI呈负相关。6、观察组中的脾肾两虚亚组与对照组相比,甘油三酯(TG)升高,有统计学差异(P<0.05)；其余血脂指标观察组各亚组与对照组相比无统计学差异(P>0.05)。7、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,收缩压(Systolic pressure)均升高,达到统计学差异(P<0.01,P<0.05)；脾肾两虚亚组的收缩压高于痰瘀兼气虚亚组,此两组间有统计学差异(P<0.05)；脾肾两虚亚组的舒张压(Diastolic pressure)与对照组相比升高,达到统计学差异(P<0.05)。8、脾肾两虚亚组和痰瘀兼气虚亚组的MMSE评分比较未达到统计学差异(P>0.05)。9、老年期痴呆患者不同年龄层次FBG、FINS、IAI、IGFBP-1、MMSE评分、TG、高密度脂蛋白－胆固醇(HDL-C)、低密度脂蛋白－胆固醇(LDL-C)和血压比较无统计学差异(P>0.05),不同年龄层次总胆固醇(T-ch)比较有统计学差异(P<0.05)。
结论：老年期痴呆与胰岛素敏感性、胰岛素样生长因子结合蛋白－1有关,脾肾两虚导致的老年期痴呆与胰岛素代谢的关系尤为密切。
Objective:To investigate the relationship and significance among insulin sensitivity (ISI)、insulin-like growth factor binding protein-1(IGFBP-1) and traditional chinese medicine syndrome of senile dementia.
Methods:Observation group and Control group,which collect patients in the wards and out-patient clinic of geriatrics division in Nanjing Durm Tower Hospital from November 2008 to July 2009. Observation group includes senile dementia patients,which is grouped by the diagnostic standard of Traditional Chinese Medicine:deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group. Control group includes patients without dementia.The fasting serum insulin (FINS) and IGFBP-1 are detected by radioimmunity and ELISA.The insulin resistance index(IAI) is calculated.We compare fasting blood glucose (FBG)、FINS、IGFBP-1、IAI、blood lipid、blood pressure and MMSE among each group.
Results:1、there is no difference of the level of fasting blood glucose among deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group and control group(P> 0.05).2、the level of serum insulin in deficiency of spleen-kidney group obstruction by phlegm-blood stasis and deficiency of Qi group are increased compared with control group,which have significant differences (P< 0.01);INS in deficiency of spleen-kidney group is higher than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is significant difference between two traditional chinese medicine syndrome types (P< 0.01).3、compared with control group, the level of insulin resisrance index in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group are decreased,which have differences(P< 0.01, P< 0.05);IAI in deficiency of spleen-kidney group is lower than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is difference between two types (P< 0.05).4、IGFBP-1 in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group are higher than in control group,which have significant differences (P< 0.01); IGFBP-1 in deficiency of spleen-kidney group is higher than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is difference between two traditional chinese medicine syndrome types(P< 0.05).5、Pearson correlation analysis show that IGFBP-1 is correlated with FBG、FINS and IAI.Among them,IGFBP-1 is positively correlated with FBG and FINS,and negatively correlated with IAI.6、Triglyceride in deficiency of spleen-kidney group is higher than in control group,which has difference(P< 0.05);other blood lipid has no difference among each group (P> 0.05).7、Systolic pressure in two TCM type are higher than in control group,there are differences (P< 0.01, P<0.05);Systolic pressure in deficiency of spleen-kidney group is highest in three groups,and there is difference between two types(P< 0.05); Diastolic pressure in deficiency of spleen-kidney group is higher than in control group,which has difference (P< 0.05).8、there is no difference of MMSE in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group(P> 0.05).9、there is no difference of FBG、FINS、IAI、IGFBP-1、MMSE、TG、HDL-C、LDL-C and blood pressure in different age(P> 0.05), there is difference of T-ch in different age (P< 0.05)
Conclusion:Senile dementia is correlated with ISI、IGFBP-1. Senile dementia which caused by deficiency of spleen-kidney has more relationshiop with the metabolism of INS.
方法：临床搜集2008年11月－2009年7月南京市鼓楼医院老年科门诊及住院病人,分为观察组和对照组。观察组为老年期痴呆患者,按中医分型标准,又分为2个亚组：脾肾两虚亚组和痰瘀兼气虚亚组。对照组为老年期非痴呆患者。运用ELISA法检测胰岛素样生长因子结合蛋白-1(IGFBP-1),放射免疫法检测空腹血清胰岛素(FINS),计算胰岛素敏感性指数(IAI),比较观察组各亚组与对照组间空腹血糖(FBG)、FINS、IAI、IGFBP-1、血脂、血压及简易智能精神状态检查量表(MMSE)评分等指标。
结果：1、观察组中的脾肾两虚亚组、痰瘀兼气虚亚组和对照组相比,FBG无统计学差异(P>0.05)。2、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,FINS升高,有显著统计学差异(P<0.01)；脾肾两虚亚组的FINS高于痰瘀兼气虚亚组,此两组之间存在显著统计学差异(P<0.01)。3、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,IAI下降,有统计学差异(P<0.01,P<0.05)；脾肾两虚亚组的IAI低于痰瘀兼气虚亚组,此两组间存在统计学差异(P<0.05)。4、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,IGFBP-1均升高,有显著统计学差异(P<0.01);脾肾两虚亚组的IGFBP-1高于痰瘀兼气虚亚组,此两组间存在统计学差异(P<0.05)。5、通过Pearson相关性分析可以看出,IGFBP-1与FBG、FINS、IAI有相关性,与FBG、FINS呈正相关,与IAI呈负相关。6、观察组中的脾肾两虚亚组与对照组相比,甘油三酯(TG)升高,有统计学差异(P<0.05)；其余血脂指标观察组各亚组与对照组相比无统计学差异(P>0.05)。7、观察组中的脾肾两虚亚组和痰瘀兼气虚亚组与对照组相比,收缩压(Systolic pressure)均升高,达到统计学差异(P<0.01,P<0.05)；脾肾两虚亚组的收缩压高于痰瘀兼气虚亚组,此两组间有统计学差异(P<0.05)；脾肾两虚亚组的舒张压(Diastolic pressure)与对照组相比升高,达到统计学差异(P<0.05)。8、脾肾两虚亚组和痰瘀兼气虚亚组的MMSE评分比较未达到统计学差异(P>0.05)。9、老年期痴呆患者不同年龄层次FBG、FINS、IAI、IGFBP-1、MMSE评分、TG、高密度脂蛋白－胆固醇(HDL-C)、低密度脂蛋白－胆固醇(LDL-C)和血压比较无统计学差异(P>0.05),不同年龄层次总胆固醇(T-ch)比较有统计学差异(P<0.05)。
结论：老年期痴呆与胰岛素敏感性、胰岛素样生长因子结合蛋白－1有关,脾肾两虚导致的老年期痴呆与胰岛素代谢的关系尤为密切。
Objective:To investigate the relationship and significance among insulin sensitivity (ISI)、insulin-like growth factor binding protein-1(IGFBP-1) and traditional chinese medicine syndrome of senile dementia.
Methods:Observation group and Control group,which collect patients in the wards and out-patient clinic of geriatrics division in Nanjing Durm Tower Hospital from November 2008 to July 2009. Observation group includes senile dementia patients,which is grouped by the diagnostic standard of Traditional Chinese Medicine:deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group. Control group includes patients without dementia.The fasting serum insulin (FINS) and IGFBP-1 are detected by radioimmunity and ELISA.The insulin resistance index(IAI) is calculated.We compare fasting blood glucose (FBG)、FINS、IGFBP-1、IAI、blood lipid、blood pressure and MMSE among each group.
Results:1、there is no difference of the level of fasting blood glucose among deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group and control group(P> 0.05).2、the level of serum insulin in deficiency of spleen-kidney group obstruction by phlegm-blood stasis and deficiency of Qi group are increased compared with control group,which have significant differences (P< 0.01);INS in deficiency of spleen-kidney group is higher than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is significant difference between two traditional chinese medicine syndrome types (P< 0.01).3、compared with control group, the level of insulin resisrance index in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group are decreased,which have differences(P< 0.01, P< 0.05);IAI in deficiency of spleen-kidney group is lower than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is difference between two types (P< 0.05).4、IGFBP-1 in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group are higher than in control group,which have significant differences (P< 0.01); IGFBP-1 in deficiency of spleen-kidney group is higher than in obstruction by phlegm-blood stasis and deficiency of Qi group,and there is difference between two traditional chinese medicine syndrome types(P< 0.05).5、Pearson correlation analysis show that IGFBP-1 is correlated with FBG、FINS and IAI.Among them,IGFBP-1 is positively correlated with FBG and FINS,and negatively correlated with IAI.6、Triglyceride in deficiency of spleen-kidney group is higher than in control group,which has difference(P< 0.05);other blood lipid has no difference among each group (P> 0.05).7、Systolic pressure in two TCM type are higher than in control group,there are differences (P< 0.01, P<0.05);Systolic pressure in deficiency of spleen-kidney group is highest in three groups,and there is difference between two types(P< 0.05); Diastolic pressure in deficiency of spleen-kidney group is higher than in control group,which has difference (P< 0.05).8、there is no difference of MMSE in deficiency of spleen-kidney group、obstruction by phlegm-blood stasis and deficiency of Qi group(P> 0.05).9、there is no difference of FBG、FINS、IAI、IGFBP-1、MMSE、TG、HDL-C、LDL-C and blood pressure in different age(P> 0.05), there is difference of T-ch in different age (P< 0.05)
Conclusion:Senile dementia is correlated with ISI、IGFBP-1. Senile dementia which caused by deficiency of spleen-kidney has more relationshiop with the metabolism of INS.
引文
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53、Jay ME.Cholinesterase inhibitors in the treatment of dementia [J].JAOA,2005,105(3):145
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58、Craft S,Asthana S，Schellenberg G,et al.Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender[J].Neuroendocrinology,1999,70 (2):146-152
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60、Chesneau V,Vekrellis K,Rosner MR,et al.Purfied recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization[J].Biochem J,2000,2:509-516
61、Gasparini L,Gouras GK,Wang R,et al.Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling[J]. J Neurosci，2001,21 (8):2561-2570
62、Blass JP,Gibson GE,Hoyer S.The role of the metabolic lesion in Alzheimer's disease [J]. J Alzheimers Dis,2002,4 (3):225-232
63、宋芳芳,张一娜,姜礼红,等.胰岛素与阿尔茨海默病关系的研究进展[J].实用老年医学,2008,22(2)：143-145
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76、Xie L,Helmerhorst E,Taddei K, et al.Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor[J].J Neuroscience,2002,22(10):RC221
77、何发毅,陈跃,黄河清.血管性痴呆患者血浆和脑脊液胰岛素含量测定[J].泸州医学院学报,2003,26(6)：542-544
78、李清春,蒋乃昌.脑内胰岛素的生物学效应[J].滨州医学院学报,2005,28(5)：350-353
79、余叶蓉.胰岛素的血管活性作用及其与内皮细胞功能的关系[J].中华内分泌代谢杂志,2002, 18(4)：323-325
80、张景丹,田芳,白凤莲.胰岛素释放实验与血管性疾病的关系[J].中外医疗,2008,27(31)：137
81、胡倡华,徐梓荣.胰岛素样生长因子结合蛋白的研究进展[J].湖南畜牧兽医,2000,(2)：2-5
82、张贺芳,苏胜偶.胰岛素样生长因子－1及其结合蛋白－1与糖尿病大血管并发症的关系[J].临床荟萃,2005,20(9)：539-541
83、李兵.胰岛素对缺血性脑损伤的保护作用[J].中风与神经疾病杂志,2000,17(4)：253-254
84、郑宇杰,戴琼,王继丰.胰岛素生长因子-1的神经保护作用研究进展[J].泸州医学院学报,2007,30(4)：339-341
85、魏平,施宗平,汪寅章,等.体外胰岛素样生长因子结合蛋白－1对人血管内皮细胞生长的抑制作用[J].第三军医大学学报,2003,25(13)：1143-1145
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51、曾秘,顾克敏,蒋英兰.阿尔茨海默病及治疗药物研究概况[J].中国药业,2006,15(6):59-61
52、肖增平,吉爱国.老年痴呆的发病机制及治疗的研究进展[J].中国老年学杂志,2008,28(1)：95-97
53、Jay ME.Cholinesterase inhibitors in the treatment of dementia [J].JAOA,2005,105(3):145
54、董永成,陈永顺,杜士明,等.抗老年痴呆药物的应用及研究进展[J].中国药房,2006,17(15)：1185-1187
55、盛树力.老年痴呆发病机理的假设[J].老年医学与保健,2005,11(4):199-201
56、盛树力.糖尿病脑病与老年性痴呆[J].中华内分泌代谢杂志,2001,17(1):58-59
57、张钦传,袁泉,林水森.胰岛素在阿尔茨海默病发病中的作用[J].中华内分泌代谢杂志,2004,20(2)：176-177
58、Craft S,Asthana S，Schellenberg G,et al.Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender[J].Neuroendocrinology,1999,70 (2):146-152
59、Boyt AA,Taddei TK,Hallmayer J,et al.The effect of insulin and glucose on the plasma concentration of Alzheimer's amyloid precursor protein[J].Neuroscience,2000,95 (3):727-734
60、Chesneau V,Vekrellis K,Rosner MR,et al.Purfied recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization[J].Biochem J,2000,2:509-516
61、Gasparini L,Gouras GK,Wang R,et al.Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling[J]. J Neurosci，2001,21 (8):2561-2570
62、Blass JP,Gibson GE,Hoyer S.The role of the metabolic lesion in Alzheimer's disease [J]. J Alzheimers Dis,2002,4 (3):225-232
63、宋芳芳,张一娜,姜礼红,等.胰岛素与阿尔茨海默病关系的研究进展[J].实用老年医学,2008,22(2)：143-145
64、Hoyer S.The brain insulin signal transduction systerm and sporadic(type Ⅱ) Alzheimers disease:an update[J].J Neural Transm,2002,109(3):341-360
65、Hoyer S,Lee SK,Loffler T,et al.Inhibition of the neuronal insulin receptor,anin vivo model for sporadic Alzheimer's disease? [J] Ann N Y Acad Sci,2000,920:256-258
66、张晓玲,丁美萍,裘秀兰,等.Alzheimer病患者与胰岛素抵抗的关系分析[J].中国临床神经科学,2003,11(2)：182-184
67、Steinberg HO, Wu YG, Hook G, et al. Insulin mediated nitric oxide production is impaired in insulin resistance[J].Diabetes,1997,46(Supplel):24A
68、王洪巨,黄元伟.胰岛素与高血压关系的实验研究[J].浙江大学学报(医学版),2003,32(1)：59-61,66
69、张鹏,李梅.原发性高血压和脑卒中患者胰岛素抵抗和脂代谢异常的初步研究[J].天津医科大学学报,2002,8(1)：63-66
70、李颖,陆莲芳,张逸强.脑卒中患者胰岛素抵抗的初步研究[J].中华神经医学杂志,2003,2(4)：302-303
71、吴根喜,唐卫华.脑梗死患者血糖及血胰岛素测定[J].郑州大学学报(医学版),2005,40(1)：154-155
72、刘洪柏,许俭兴,区丽明.胰岛素抵抗与脑卒中关系的研究现状[J].中国临床康复,2003,7(28)：3864-3866
73、魏平.胰岛素样生长因子结合蛋白－1(IGFBP-1)研究进展[J].国外医学分子生物学分册,2002,24(5)：269-272
74、陈玉静,田金洲.阿尔茨海默病是另外一种形式的糖尿病[J].中国老年学杂志,2008,28(4)：402-404
75、武月萍,田金洲.胰岛素抵抗与阿尔茨海默病[J].中国老年学杂志,2005,25(3)：348-350
76、Xie L,Helmerhorst E,Taddei K, et al.Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor[J].J Neuroscience,2002,22(10):RC221
77、何发毅,陈跃,黄河清.血管性痴呆患者血浆和脑脊液胰岛素含量测定[J].泸州医学院学报,2003,26(6)：542-544
78、李清春,蒋乃昌.脑内胰岛素的生物学效应[J].滨州医学院学报,2005,28(5)：350-353
79、余叶蓉.胰岛素的血管活性作用及其与内皮细胞功能的关系[J].中华内分泌代谢杂志,2002, 18(4)：323-325
80、张景丹,田芳,白凤莲.胰岛素释放实验与血管性疾病的关系[J].中外医疗,2008,27(31)：137
81、胡倡华,徐梓荣.胰岛素样生长因子结合蛋白的研究进展[J].湖南畜牧兽医,2000,(2)：2-5
82、张贺芳,苏胜偶.胰岛素样生长因子－1及其结合蛋白－1与糖尿病大血管并发症的关系[J].临床荟萃,2005,20(9)：539-541
83、李兵.胰岛素对缺血性脑损伤的保护作用[J].中风与神经疾病杂志,2000,17(4)：253-254
84、郑宇杰,戴琼,王继丰.胰岛素生长因子-1的神经保护作用研究进展[J].泸州医学院学报,2007,30(4)：339-341
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