12-脂氧合酶抑制剂黄芩素对2型糖尿病大鼠肾脏细胞外基质的影响及机制

目的：探讨12-脂氧合酶（12-lipoxygenase，12-LO）特异性抑制剂黄芩素（baicalein，BAI）对2型糖尿病大鼠肾脏细胞外基质（ECM）的影响及机制。方法：将链脲佐菌素（streptozotocin，STZ）诱导的2型糖尿病大鼠随机分为：对照组、模型组、黄芩素低剂量治疗组（80mg·kg^-1·d^-1）和高剂量治疗组（160mg·kg^-1·d^-1）。治疗12周后检测各组大鼠尿白蛋白排泄率（UAER）、血糖（BG）、血肌酐（Scr）、血尿素氮（BUN）、内生肌酐清除率（Ccr）等变化；应用免疫组化技术检测各组肾组织中胶原Ⅳ（ColⅣ）、纤维连接蛋白（FN）、层黏连蛋白（LN）的表达；应用RT—PCR方法检测12-LOmRNA的表达。结果：治疗组较模型组明显改善尿白蛋白、BUN水平和肾脏肥大指数等。与对照组比较，模型组大鼠肾脏ColⅣ、FN、LN的表达明显增加；治疗组可明显降低糖尿病大鼠肾脏ColⅣ、FN、LN的表达。12-LOmRNA的相对含量模型组明显高于对照组（P＜0．01）；低、高剂量治疗组较模型组显著降低（P＜0．01）。两治疗组之间各指标无统计学差异。结论：BAI对2型糖尿病大鼠肾脏具有明显的保护作用，其机制可能是通过抑制12-LOmRNA的表达，从而下调肾脏ColⅣ、FN、LN的表迭，减少ECM沉积，延缓糖尿病肾病的发生、发展。

Effect and Mechanism of Baicalein on Extracellular Matrix of Kidney in Type 2 Diabetic Rats

To explore the effects of BAI on extracellular matrix of kidney and probable mechanism in type 2 diabetic rats. Methods：Streptozotocin induced diabetic rats were randomly assigned to four groups： control group, type 2 diabetic model group and BAI treated group s（80 rag·kg^- 1. d^-1 or 160 rag. kg^- 1. d^- 1 respectively）. After 12 weeks, the expression of ColⅣ, FN and LN in the renal tissue of type 2 diabetic rats was detected by immunohistochemistry. In addition,BG,Scr、BUN、Ccr and UAER were measured respectively. 12- Lipoxygenase gene expression was studied with RT- PCR. Results： Compared to diabetic model group, the levels of UAER,Scr,BUN, kidney/weigh in BAI treated groups were significantly decreased, and the expressions of Col Ⅳ ,FN and LN increased in the renal tissue of type 2 diabetic rats（P〈0.01）. BAI could significantly reduce the expression of Col IV ,FN and LN in the renal tissue of diabetic rats （P〈0.01）. 12 - LO mRNA was significantly increased in the renal tissue of diabetic rats. The expression level of 12 - LO mRNA was obviously down - regulated in BAI treated group. All indices in the two treatment groups have no significant difference. Conclusion：BAI can not decrease the blood sugar, by inhibiting the expression of 12 - LO mRNA and down- regulating the expression of ColⅣ, FN and LN in renal tissue. It can significantly relieve ECM accumulation and it may be hopefully served as a useful strategy for prevention and treatment of diabetic nephropathy.