姜黄素对糖尿病大鼠肾脏保护作用的机制研究

目的 探讨姜黄素对实验性糖尿病大鼠肾脏基质金属蛋白酶-2（matrix metalloproteinase-2,MMP-2）及其抑制物金属蛋白酶-2组织抑制物（tissue inhibitor of metalloproteinase-2,TIMP-2）表达的影响.方法 大鼠随机分为正常对照组（A组）、糖尿病组（B组）及姜黄素治疗组（C组）,采用腹腔单剂量注射链脲佐菌素（streptozotocin,STZ）65 mg/kg建立糖尿病大鼠模型.治疗组给予姜黄素30 mg·kg-1·d-1腹腔注射.实验第3、6周各组分别宰杀6只大鼠,并检测24 h尿白蛋白排泄率（urinary albumin excretion rate,UAER）、肌酐清除率（creatinine clearance rate,Ccr）及肾重/体重.采用免疫组织化学染色法检测肾小球MMP-2、TIMP-2、纤维连接蛋白（fibronectin,FN）和Ⅳ型胶原表达.结果 治疗组大鼠UAER（P〈0.05或〈0.01）、Ccr（P〈0.05）、肾重/体重（P〈0.05）均明显低于糖尿病组大鼠.免疫组织化学染色可见糖尿病大鼠肾小球TIMP-2、 FN和Ⅳ型胶原表达均明显增加（P〈0.05或〈0.01）,治疗组上述指标的表达均受到明显抑制（P〈0.05）.MMP-2在糖尿病大鼠肾小球的表达明显被抑制（P〈0.01）,治疗组其表达明显增加（P〈0.05）.结论 姜黄素通过上调糖尿病大鼠肾小球MMP-2表达、下调TIMP-2表达,对糖尿病大鼠肾脏病变具有保护作用.

Study on the action mechanism of protective effects of curcumin on kidney of experimental diabetic rats

Objective To investigate the action mechanism of protective effects of curcumin on kidney of experimental diabetic rats, by observing the effects of curcumin on the expression of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （ TIMP-2 ） in kidney of experimental diabetic rats. Methods The rats were randomly divided into normal control group （ group A） , diabetes group （group B ） and curcumin treatment group （group C） ,The rat models of diabetes were established by intraperitoneal injection with eurcumin 60mg/kg. The rats in curcumin treatment group were given curcumin 30mg · kg^-1 ·d^-1 intraperitoneally. The UAER, Ccr and the ratio of kidney weight/body weight were detected after 3-week and 6-week treatment, and the expressions of MMP-2, TIMP-2, FN and collagen Ⅳ were measured by immunohistological staining. Results The UAER, Ccr and the ratio of kidney weight/body in group C were significantly lower than those in group B （ P 〈 0.05 or P 〈 0. 01 ）. As composed with those in group C, the protein expressions of TIMP-2, FN and collagen Ⅳ were significantly increased in glomeruli of the rats in group B（ P 〈0.05 orP 〈0.01 ）. The expression of MMP-2 was significantly decreased in group B, however, which was obviously increased in group C （ P 〈 0. 05 ）. Conclusion The curcumin has protective effects on the kidney of experimental diabetic rats by up-regulating the expression of MMP-2 and down-regulating the expression of TIMP-2 in glomeruli of diabetic rats.