【摘要】 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(80 mg·kg-1·d-1)和高剂量治疗组(160 mg·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-LO mRNA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-LO mRNA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-LO mRNA的表达,从而下调肾脏ColⅣ、FN、LN的表达,减少ECM沉积,延缓糖尿病肾病的发生、发展。更多还原

【Abstract】 Objective: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 mg·kg-1·d-1 or 160 mg·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 ColⅣ,FN and LN increased in the renal tissue of type 2 diabetic rats(P<0.01).BAI could significantly reduce the expression of ColⅣ,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.更多还原