青蒿素对糖尿病大鼠肾脏保护作用机制研究

目的探讨青蒿素对糖尿病大鼠肾基质金属蛋白酶-2（MMP-2）及其抑制物金属蛋白酶-2组织抑制物（TIMP-2）表达的调节作用。方法将大鼠随机分为对照组（A组）、糖尿病非治疗组（B组）及糖尿病青蒿素治疗组（C组）,采用腹腔单剂量注射链脲佐菌素（STZ）65 mg/kg方法以建立糖尿病大鼠模型。C组给予青蒿素300 g/（kg·d）腹腔注射。实验进行到第3周、第6周时3组分别宰杀大鼠6只,检测肾质量/体质量、24 h尿白蛋白排泄率（UAER）及肌酐清除率（Ccr）。用免疫组化染色方法分别检测肾小球Ⅳ型胶原、TIMP-2、MMP-2和纤维连接蛋白（FN）表达情况。结果 C组大鼠Ccr、UAER、肾质量/体质量均显著低于B组（P〈0.05或0.01）。免疫组化染色证明糖尿病大鼠肾小球Ⅳ型胶原、FN和TIMP-2表达都明显上调（P〈0.05或0.01）,C组上述指标的表达都被显著抑制（P〈0.05）。MMP-2在B组大鼠肾小球的表达显著下调（P〈0.01）,C组其表达显著上调（P〈0.05）。结论青蒿素通过抑制糖尿病大鼠肾小球TIMP-2表达及增加MMP-2表达,从而保护糖尿病实验大鼠肾脏功能。

Study on the mechanism of renoprotective effects of artemisinin in diabetic rats

Objective It is to explore the regular effect of artemisinin on the expression of MMP- 2 and TIMP- 2 in diabetic rats. Methods The rats were randomly divided into control group（ A group）,diabetic group with nontreatment（ B group）,diabetic group treated with artemisinin（ C group）. The diabetic rat models were established by intraperitoneal injection with STZ 65 mg /kg. Group C was given artemisinin 300 g /（ kg·d） by intraperitoneal injection. 6 rats in the three groups were killed to determine kidney weight / body weight,Ccr,UAER after 3 and 6 weeks of treatment with artemisinin,meanwhile FN,TIMP- 2,collagen Ⅳ protein and MMP- 2 expressions were measured by immunohistological staining. Results Ccr,UAER and kidney /body weight ratio in the rats of group C were significantly lower than those of the rats in group B（ P〈0. 05 or 0. 01）. Immunohistological staining showed that the protein expressions of FN,collagen Ⅳ and TIMP- 2 significantly increased in glomeruli,while MMP- 2 protein significantly decreased in diabetic rats（ P〈0. 05 or 0. 01）. The abnormal level of these proteins was partly reversed in group C（ P〈0. 05）. Conclusion Artemisinin has some renoprotective effects in diabetic rats,partly through upregulation MMP- 2 and downregulation TIMP- 2 activity in glomeruli.