TAX1 BP1减轻链脲佐菌素诱导的糖尿病心肌病心肌纤维化的机制研究

摘要

Objective To investigate the mechanism of TAX 1BP1 on cardiac fibrosis in mice model of DCM.Methods Mice were subjected to STZ injection to induce type 1 DCM model.12 weeks after final injection, mice were subjected to myocardial injection of advurus-TAX1BP1 to overexpress TAX1BP1.At 16 weeks after final STZ injection , hearts were removed.Immunohistochemical staining was used to assess CD31,α-SMA expression level.Immunofluorescence staining was used to assess vascular endothelial (VE)-cadherin, collagen Ⅲ expression.Western blot was used to detect VE-cadherin, CD31, α-SMA, and vimentin expression level in each group .Results The microvascular density assessed by CD 31 staining was significantly decreased in the model group , while increased in the TAX1BP1 overexpression model group (P<0.05).The expression of α-SMA in the model group was higher than that in the control group , which was decreased in TAX1BP1 overexpression-model group (P<0.05).Double fluorescence labeling result showed that compared with the control group , the expression of VE-cadherin was decreased and collagen Ⅲwas increased in the model group (P<0.05).These was changed by TAX1BP1 overexpression.Western blot showed that the expression of VE-cadherin and CD31 were decreased , α-SMA and vimentin were increased in the model group. These was also changed by TAX1BP1 overexpression ( P<0.05 ) . Conclusion TAX1BP1 may suppress the development of cardiac fibrosis in the diabetic process by inhibiting endothelin mesenchymal transformation .%目的 探讨TAX1 BP1是否通过抑制内皮向间质转化保护糖尿病心肌病中纤维化的发展.方法 采用链脲佐菌素(STZ)腹腔注射的方法建立1型糖尿病心肌病的小鼠模型,12周后采用腺病毒心肌注射的方式过表达TAX1BP1基因,16周后取小鼠心脏.采用免疫组化染色CD31检测微血管密度,平滑肌动蛋白α(α-SMA)染色检测纤维化激活程度;采用免疫印迹法检测上述蛋白的表达水平.结果 模型组小鼠心脏CD31标记的微血管密度显著降低,TAX1BP1过表达-模型组微血管密度增加(P<0.05);模型组小鼠心脏α-SMA染色表达较对照组增加,TAX1BP1过表达-模型组α-SMA染色表达较模型组降低(P<0.05);双荧光标记结果显示:与对照组相比,模型组小鼠心脏内皮细胞钙黏蛋白表达降低,而波形蛋白表达显著增加;与模型组相比,TAX1BP1过表达-模型组内皮细胞钙黏蛋白表达增加,而波形蛋白表达显著降低(P<0.05).免疫印迹结果与染色结果一致,与对照组相比,模型组小鼠心脏内皮细胞钙黏蛋白、CD31表达降低,而α-SMA、波形蛋白表达显著增加;与模型组相比,TAX1BP1过表达-模型组内皮细胞钙黏蛋白、CD31表达增加,而α-SMA、波形蛋白表达显著降低(P<0.05).结论 TAX1BP1可能通过抑制内皮向间质转化阻止糖尿病心肌纤维化的发展.