牛初乳短链胰岛素样生长因子-1对糖尿病大鼠肾脏的保护作用及其机制研究
作者：游利 俞茂华 叶红英 杨秀芳 颜贻谦 钟慈声
单位：游利(200040 上海医科大学附属华山医院内分泌科)；俞茂华(200040 上海医科大学附属华山医院内分泌科)；叶红英(200040 上海医科大学附属华山医院内分泌科)；杨秀芳(200040 上海医科大学附属华山医院内分泌科)；颜贻谦(中国科学院上海生理所)；钟慈声(上海医科大学电镜室)
关键词：糖尿病；肾脏；胰岛素样生长因子
中华肾病杂志000412摘 要：目的 观察牛初乳短链胰岛素样生长因子-1(BCtlGF-1)对糖尿病肾病的保护作用及探讨其可能的作用机制。方法 采用生化法、放射免疫法、荧光分析法及逆转录-聚合酶链式反应(RT-PCR)技术等进行研究。结果 (1)糖尿病治疗组的空腹血糖、甘油三酯、果糖胺明显低于糖尿病对照组；(2)糖尿病治疗组24h尿白蛋白排泄率、24h尿量、24h内生肌酐清除率低于糖尿病对照组；(3)电镜观察大鼠”肾脏病理切片发现BCtICP-1对糖尿病大鼠肾脏损害有改善作用；(4)糖尿病对照组肾组织IGF-1mRNA表达明显低于正常对照组，糖尿病对照组与糖尿病治疗组无明显异常；(5)糖尿病治疗组肾组织胶原含量及糖基化终末产物(AGEs)、尿血栓素B2/6-酮-前列环素 1α(TXB2/6-keto-PGF1α)低于糖尿病对照组。结论 (1)BCtIGF-1可以明显降低STZ糖尿病大鼠的血糖、血脂；(2)BCtIGF-1不会引起肾皮质IGF-1mRNA表达的增加；(3)BCtIGF-1对STZ糖尿病大鼠肾脏有保护作用，其保护机制是由于BCtIGF-1对血糖、血脂的改善；此外，可能与其减少肾组织胶原及AGEs含量，改善前列腺素—血栓素合成的不平衡有关。
, 百拇医药
The protective effects of bovine colostrum truncated IGF-I on kidney of diabetic rats and the study of mechanism
YOU Li ,YU Maohua ,YE Hongying
(Department of Endocrinology, Huashan Hospital,Shanghai Medical Univeristy, Shanghai 200040, China)
Abstract：Objective To observe the effect of BCtIGF-1 on diabetic nephropathy and explore its mechanism.Methods Techniques including biochemistry,radioimmunoassay,fluoroassays,molecular biology(RT-PCR) were used in this study. Results (1) Serum FBG,TG and FMN concentrations in BCtIGF-1 groups were significantly lower than those of diabetic control group;(2) 24h UAER, 24h urinary volume in BCtIGF-1 groups were significantly lower than those of diabetic control group; (3) BCtIGF-1 had protective effect on diabetic nephropathy by observing the kidney tissues with electron microscope;(4)Kidney IGF-1 mRNA in diabetic control group was significantly lower than that of normal control group,no differences were found between diabetic control group and BCtIGF-1 groups;(5) Collagen and AGEs of kidney tissue,urinary TXB2/6-keto-PGF1αin BCtIGF-1 groups were significantly lower than those of diabetic control group;Conclusions (1) BCtIGF-1 has hypoglycemic and hypolipidic effects; (2) BCtIGF-1 does not increase the level of IGF-1 mRNA in kidney tissue; (3)BCtIGF-1 might have protective effect on diabetic nephropathy.The protective mechanism may be associated with its hypoglycemic and hypolipidic effects;in addition,it might relate to the improvement of PGI2-TXA2 synthetic imbalance and the reduction of the collagen and AGEs levels in kidney tissue.
, 百拇医药
Keywords：Diabetes; Kidney; Insulin-like growth factor
参考文献：
[1]Hirschberg R,Adler S.Insulin-like growth factor system and the kidnev:physiology,pathophysiology and therapeutic implications.Am J Kidney Dis,1998,31:901-918.
[2]Cheng W,Reiss K,Kajstura J,et al.Down-regulation of the IGF-1 system parallels the attenuation in the proliferative capacity of ventricular myocytes during postnatal development.Lab Invest,1995,72:646-655.
, 百拇医药
[3]Terada Y,Tamita K,Nonoguchi H,et al.Expression of endothelin3mRNA along rat nephron segments using polymerase chain reaction.Kidnty Int,1993,44:1273-1279.
[4]Monnier VM,Kohn KR,Cerami A.Accelerated age-related browning of human collagen in diabetes mellitus.Proc Natl Acad Sci USA,1984,81:583-601.
[5]Hermann S,Karlbeinz S.Determination of hydroxyproline.Clin Chim Acta,1967,18:267-273.
[6]Eveol JD,Underword LE.Estimation of tissue concentration of somatomedia C/insulin-like growth factor 1.Methods Enzymol 1987,146:227-233.
, 百拇医药
[7]Acerini CL,Patton CM,Sowage MO,et al.Randomised placebo-controlled trial of human recombinat insulin-like growth factor 1 plus intensive insulin therapy in adolescents with insulin-like dependent diabetes mellitus.Lancet,1997,350:1199-1204.
[8]Doi T,Striker LJ,Carter C,et al.Glomerular lessions in mice transgenic for growth hormone and insulin-like growth factor 1 relationship between increased glomerular size and mesangial sclerosis.Am J Pathol,1990,137:541-542.
, 百拇医药
[9]Flyvberg A,Frystyr J,Thorlacius HO,et al.Somatostation analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats.Diabetologia,1989,32:261-265.
[10]Dunger DB,Checth JD.Growth hormone insulin-like growth factor axis in insulin-dependent diabetes mellitus.Horm Res,1996,46:2-6.
[11]Schambelan M,Blake S,Straer J,et al.Increased prostaglandin production by glomeruli isolated from rats with streptozotocin induced diabetes mellitus. J Clin, Ivest,1985,75:404-412.
, 百拇医药
[12]Perico N,Benigni A,Gabanelli M,et al.Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperfusion of diabetic rats.Diabetes,1992,41:533-538.
[13]Crave PA,Caines MA,Derubertis FR.Sequential alteration in glomerular prostaglandin and thromboxane synthesis in diabetic rats:relationship to the hyperfiltration of early diabetes.Metabolism,1987,36:95-103.
收稿日期：1999-06-29, http://www.100md.com
单位：游利(200040 上海医科大学附属华山医院内分泌科)；俞茂华(200040 上海医科大学附属华山医院内分泌科)；叶红英(200040 上海医科大学附属华山医院内分泌科)；杨秀芳(200040 上海医科大学附属华山医院内分泌科)；颜贻谦(中国科学院上海生理所)；钟慈声(上海医科大学电镜室)
关键词：糖尿病；肾脏；胰岛素样生长因子
中华肾病杂志000412摘 要：目的 观察牛初乳短链胰岛素样生长因子-1(BCtlGF-1)对糖尿病肾病的保护作用及探讨其可能的作用机制。方法 采用生化法、放射免疫法、荧光分析法及逆转录-聚合酶链式反应(RT-PCR)技术等进行研究。结果 (1)糖尿病治疗组的空腹血糖、甘油三酯、果糖胺明显低于糖尿病对照组；(2)糖尿病治疗组24h尿白蛋白排泄率、24h尿量、24h内生肌酐清除率低于糖尿病对照组；(3)电镜观察大鼠”肾脏病理切片发现BCtICP-1对糖尿病大鼠肾脏损害有改善作用；(4)糖尿病对照组肾组织IGF-1mRNA表达明显低于正常对照组，糖尿病对照组与糖尿病治疗组无明显异常；(5)糖尿病治疗组肾组织胶原含量及糖基化终末产物(AGEs)、尿血栓素B2/6-酮-前列环素 1α(TXB2/6-keto-PGF1α)低于糖尿病对照组。结论 (1)BCtIGF-1可以明显降低STZ糖尿病大鼠的血糖、血脂；(2)BCtIGF-1不会引起肾皮质IGF-1mRNA表达的增加；(3)BCtIGF-1对STZ糖尿病大鼠肾脏有保护作用，其保护机制是由于BCtIGF-1对血糖、血脂的改善；此外，可能与其减少肾组织胶原及AGEs含量，改善前列腺素—血栓素合成的不平衡有关。
, 百拇医药
The protective effects of bovine colostrum truncated IGF-I on kidney of diabetic rats and the study of mechanism
YOU Li ,YU Maohua ,YE Hongying
(Department of Endocrinology, Huashan Hospital,Shanghai Medical Univeristy, Shanghai 200040, China)
Abstract：Objective To observe the effect of BCtIGF-1 on diabetic nephropathy and explore its mechanism.Methods Techniques including biochemistry,radioimmunoassay,fluoroassays,molecular biology(RT-PCR) were used in this study. Results (1) Serum FBG,TG and FMN concentrations in BCtIGF-1 groups were significantly lower than those of diabetic control group;(2) 24h UAER, 24h urinary volume in BCtIGF-1 groups were significantly lower than those of diabetic control group; (3) BCtIGF-1 had protective effect on diabetic nephropathy by observing the kidney tissues with electron microscope;(4)Kidney IGF-1 mRNA in diabetic control group was significantly lower than that of normal control group,no differences were found between diabetic control group and BCtIGF-1 groups;(5) Collagen and AGEs of kidney tissue,urinary TXB2/6-keto-PGF1αin BCtIGF-1 groups were significantly lower than those of diabetic control group;Conclusions (1) BCtIGF-1 has hypoglycemic and hypolipidic effects; (2) BCtIGF-1 does not increase the level of IGF-1 mRNA in kidney tissue; (3)BCtIGF-1 might have protective effect on diabetic nephropathy.The protective mechanism may be associated with its hypoglycemic and hypolipidic effects;in addition,it might relate to the improvement of PGI2-TXA2 synthetic imbalance and the reduction of the collagen and AGEs levels in kidney tissue.
, 百拇医药
Keywords：Diabetes; Kidney; Insulin-like growth factor
参考文献：
[1]Hirschberg R,Adler S.Insulin-like growth factor system and the kidnev:physiology,pathophysiology and therapeutic implications.Am J Kidney Dis,1998,31:901-918.
[2]Cheng W,Reiss K,Kajstura J,et al.Down-regulation of the IGF-1 system parallels the attenuation in the proliferative capacity of ventricular myocytes during postnatal development.Lab Invest,1995,72:646-655.
, 百拇医药
[3]Terada Y,Tamita K,Nonoguchi H,et al.Expression of endothelin3mRNA along rat nephron segments using polymerase chain reaction.Kidnty Int,1993,44:1273-1279.
[4]Monnier VM,Kohn KR,Cerami A.Accelerated age-related browning of human collagen in diabetes mellitus.Proc Natl Acad Sci USA,1984,81:583-601.
[5]Hermann S,Karlbeinz S.Determination of hydroxyproline.Clin Chim Acta,1967,18:267-273.
[6]Eveol JD,Underword LE.Estimation of tissue concentration of somatomedia C/insulin-like growth factor 1.Methods Enzymol 1987,146:227-233.
, 百拇医药
[7]Acerini CL,Patton CM,Sowage MO,et al.Randomised placebo-controlled trial of human recombinat insulin-like growth factor 1 plus intensive insulin therapy in adolescents with insulin-like dependent diabetes mellitus.Lancet,1997,350:1199-1204.
[8]Doi T,Striker LJ,Carter C,et al.Glomerular lessions in mice transgenic for growth hormone and insulin-like growth factor 1 relationship between increased glomerular size and mesangial sclerosis.Am J Pathol,1990,137:541-542.
, 百拇医药
[9]Flyvberg A,Frystyr J,Thorlacius HO,et al.Somatostation analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats.Diabetologia,1989,32:261-265.
[10]Dunger DB,Checth JD.Growth hormone insulin-like growth factor axis in insulin-dependent diabetes mellitus.Horm Res,1996,46:2-6.
[11]Schambelan M,Blake S,Straer J,et al.Increased prostaglandin production by glomeruli isolated from rats with streptozotocin induced diabetes mellitus. J Clin, Ivest,1985,75:404-412.
, 百拇医药
[12]Perico N,Benigni A,Gabanelli M,et al.Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperfusion of diabetic rats.Diabetes,1992,41:533-538.
[13]Crave PA,Caines MA,Derubertis FR.Sequential alteration in glomerular prostaglandin and thromboxane synthesis in diabetic rats:relationship to the hyperfiltration of early diabetes.Metabolism,1987,36:95-103.
收稿日期：1999-06-29, http://www.100md.com