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目的:探讨热休克蛋白47（HSP47）对链脲佐菌素（STZ）诱导的糖尿病心肌病的影响及具体机制。方法:采用8~10周龄C57BL/6雄性小鼠，随机分为对照组、HSP47过表达对照组、糖尿病组、HSP47过表达糖尿病组，每组12只。通过STZ腹腔注射的方法建立1型糖尿病心肌病小鼠模型，造模成功8周后应用小鼠尾静脉注射的方式过表达HSP47基因，6周后每组取出小鼠心脏6只用于病理和分子生物学分析。应用苏木精-伊红（HE）染色和天狼星红（PSR）染色分别检测心肌细胞横截面积和心肌组织纤维化程度；应用CD31和Ⅰ型胶原蛋白免疫荧光染色检测纤维化程度；采用免疫印迹法测定纤维化相关蛋白的表达水平。结果:与对照组比较，糖尿病组小鼠心肌HSP47表达水平上调（2.014±0.264比1.004±0.064，n P<0.001）。糖尿病组小鼠心肌细胞横截面积较对照组增加[（235.3±20.7）μmn 2比（172.8±13.6）μmn 2，n P<0.001]，HSP47过表达糖尿病组的心肌细胞横截面积进一步增加[（302.2±41.0）μmn 2比（235.3±20.7）μmn 2，n P=0.009]。同时，小鼠心肌肥厚标志物心房钠尿肽（ANP）、脑钠肽（BNP）、肌球蛋白重链β（β-MHC）mRNA表达水平进一步上调（均n P<0.001）。与对照组比较，糖尿病组小鼠心肌胶原纤维含量增加[（7.333±1.127）%比（4.837±0.775）%，n P=0.002]，HSP47过表达糖尿病组的心肌纤维含量进一步增加[（9.175±1.008）%比（7.333±1.127）%，n P=0.025]，同时纤维化指标Ⅰ型胶原蛋白、Ⅲ型胶原蛋白、结缔组织生长因子（CTGF）和转化生长因子β（TGFβ）的mRNA水平进一步上调（均n P<0.001）。Western印迹结果显示，与糖尿病组相比，HSP47过表达糖尿病组Smad3的磷酸化水平上调，同时α-平滑肌肌动蛋白（α-SMA）和TGFβ的蛋白水平增加（n P<0.001）。n 结论:HSP47可通过激活TGFβ/Smad3信号通路恶化STZ诱导的糖尿病心肌纤维化。“,”Objective:To investigate the effect and specific mechanism of heat shock protein 47 (HSP47) on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM).Methods:A mouse model of type 1 diabetic cardiomyopathy was established by intraperitoneal injection of STZ. After 8 weeks of successful modeling, HSP47 was overexpressed by tail vein injection, and the heart of the mouse was harvested after 6 weeks. Hematoxylin-eosin (HE) staining and Sirius red (PSR) staining were used to detect the cross-sectional area of myocardial cells and myocardial fibrosis, respectively. Immunofluorescence staining with α-smooth muscle actin (α-SMA) and collagen Ⅰ was used to detect the degree of fibrosis activation. The expression level of fibrosis-related proteins was determined by Western blot.Results:The expression level of HSP47 in the myocardium of the diabetic group up-regulated (2.014±0.264 vs 1.004±0.064, n P<0.001). The area of myocardial cells in the diabetic group was increased compared with the control group [(235.3±20.7) μm n 2 vs (172.8±13.6) μm n 2, n P<0.001] and the cross-sectional area of myocardial cells in the HSP47 overexpression-diabetes group was further increased [(302.2±41.0) μm n 2 vs (235.3±20.7) μm n 2, n P=0.009], while the mRNA levels of mouse cardiac hypertrophic markers atrial natriuretic peptide (ANP), type B brain natriuretic peptide (BNP), myosin heavy chain β (β-MHC) further upregulated (all n P<0.001). Compared with the control group, the myocardial fibrosis content in the diabetic group increased [(7.333±1.127)% vs (4.837±0.775)%, n P=0.002] and the left ventricular fibrosis content of the HSP47 overexpressing diabetic group further increased [(9.175±1.008)% vs (7.333±1.127)%, n P=0.025] and the mRNA levels of fibrosis index collagenⅠ, collagen Ⅲ, connective tissue growth factor (CTGF) and transforming growth factor β (TGFβ) further up-regulated (all n P<0.001). Immunofluorescence results showed that compared with the control group, the expression of collagenⅠ up-regulated in the endothelial stroma of the diabetic group and the content of collagenⅠ in the HSP47 over-expressing diabetic group was higher (n P<0.001). Western blot results indicated that the phosphorylation level of Smad3 and the protein levels of α-SMA and TGFβ in HSP47 overexpressing diabetic group increased, compared with those of diabetic group (all n P<0.001).n Conclusion:HSP47 ameliorates STZ-induced diabetic myocardial fibrosis by activating the TGFβ/Smad3 signaling pathway.