目的 探讨葛根素对糖尿病大鼠肾小球结构、功能及肾组织基质金属蛋白酶 10 (MMP-10)、基质金属蛋白酶组织抑制剂 1(TIMP-1)表达的影响。方法 ip链脲佐菌素 (6 5 mg/ kg)诱发糖尿病大鼠模型,每日 ip葛根素注射液,共 16周。给药结束后,收集尿液,测定尿蛋白 (Upro),尿肌酐 (U cr)含量;腹主动脉取血,测定血糖(Glu),血肌酐 (Scr),尿素氮 (BU N)含量;采用原位杂交法检测肾小球 MMP-10,TIMP-1m RNA表达,流式细胞术和免疫组化检测肾皮质 MMP-10、TIMP-1及 型胶原、层黏连蛋白 (L N)表达。结果 糖尿病组较对照组肾小球 MMP-10、TIMP-1m RNA及蛋白表达增加,肾皮质 MMP-10,TIMP-1及 型胶原、L N表达亦增加;反映肾功能的各项生化指标水平升高。葛根素用药组较糖尿病组 MMP-10、TIMP-1m RNA、蛋白及 型胶原、L N表达减少;肾功能有所改善。结论 葛根素对糖尿病大鼠肾结构功能具有保护作用,除降低血糖外,调节肾小球 MMP-10,TIMP-1表达从而减轻肾小球细胞外基质沉积也可能是其作用途径之一。

Object To investigate the effects of puerarin on renal structure, function and expressions of matrix metalloproteinase 10 (MMP 10) and tissue inhibitor of melalloproteinase 1 (TIMP 1) in the kidney of diabetic rats. Methods Uninephrectomized male Wistar rats were used to induce diabetic models by ip Streptozocin (65 mg/kg). Puerarin was given daily by ip from the third day of induction to diabetes for 16 weeks. Then, Upro, Ucr in urine and Glu, Scr, BUN in serum were determined. Situ hybridization and immunohistochemistry were used to detect MMP 10, TIMP 1 mRNA expressions and MMP 10, TIMP 1, collagen Ⅳ and Laminin (LN) expressions in renal glomeruli with image analysis system; flow cytometry was used to detect the expressions of MMP 10, TIMP 1 of renal cortex. Results BUN, Ccr, and Upro in diabetic rats were significant higher than that in control group. Compared with those in kidneys of control group, diabetic kidneys showed increased expressions of both MMP 10, TIMP 1 mRNA, proteins and excessive deposition of glomeruli extracellular matrix. Glu and the level of expressions of MMP 10, TIMP 1, collagen Ⅳ, and LN were reduced by puerarin treatment, renal function was improved. Conclusion Puerarin has some renal protective effect on diabetic nephropathy partly through inhibition of excessive deposition of glomeruli extracellular matrix by down regulating MMP 10 and TIMP 1 expressions besides reducing Glu.

教育部归国博士基金资助项目(980601)