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突变型生长激素(GH)转基因小鼠,是一个去GH的动物模型.本项研究利用这种转基因小鼠对GH在糖尿病肾病发病中的作用进行了研究.我们首先用STZ诱导出糖尿病,进而对其肾小球的形态、结构和细胞外基质的沉积加以分析,并采用肾小球微分离技术、逆转录和竞争性PCR对肾小球α1(N)型胶原、层粘蛋白β1、72kDN型胶原酶、金属蛋白酶的组织抑制因子-3(TIMP-3)和转化生长因子-β(TGF-β)mRNA的表达进行了定量分析。结果发现这种转基因小鼠在糖尿病的情况下,不仅组织学上肾小球无异常,肾小球α1(N)型胶原和层粘蛋白B1mRNA的表达也是正常的.这点与免疫荧光染色结果完全相符.有趣的是,尽管该模型肾小球无病变,但其肾小球内72kDN型胶原酶、T■MP-3和TGF-β基因的表达,在高血糖的状态下仍呈上调状态。提示其在糖尿病肾病发病中的作用,有待进一步阐明.
Mutant growth hormone (GH) transgenic mice, an animal model of GH. In this study, the role of GH in the pathogenesis of diabetic nephropathy was studied using this transgenic mouse. We first induced diabetes mellitus with STZ, and then analyzed the morphology, structure and extracellular matrix deposition of glomeruli, and used glomerular microdissection technique, reverse transcription and competitive PCR to detect glomerular α1 (N) Type collagen, laminin β1, 72kDN type collagenase, tissue inhibitor of metalloproteinase-3 (TIMP-3) and transforming growth factor-β (TGF-β) mRNA were quantitatively analyzed. As a result, it was found that, in the case of diabetes, such a transgenic mouse is not only histologically abnormal in glomeruli but also normal in expression of glomerular α1 (N) type collagen and laminin B1 mRNA. This is exactly the same with the results of immunofluorescence staining. Interestingly, although the model glomerular disease-free, but its glomerular 72kDN type collagenase, T ■ MP-3 and TGF-β gene expression in hyperglycemic state was still upregulated. Suggesting its role in the pathogenesis of diabetic nephropathy needs further elucidation.