【摘要】 目的：探讨补阳还五汤对糖尿病心肌病（DCM）小鼠心肌组织保护作用及炎症和凋亡因子的影响。方法：30只7～8周龄db/db小鼠饲养至10周使其发展为DCM并随机分为模型组、补阳还五汤组、舒洛地特组，每组10只。7～8周龄db/m组小鼠10只作为对照组。给予相应药物治疗12周后，检测小鼠血糖（FBG）、肌酸激酶同工酶（CK-MB）、白细胞介素-6(IL-6)、单核细胞趋化因子-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、甘油三脂（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平；qRT-PCR检测Toll样受体4(TLR4)、核转录因子-κB p65(NF-κB p65)mRNA表达；Western Blot检测小鼠心脏组织TLR4、NF-κB p65、Cleaved caspase-3和Cleaved PARP蛋白表达；免疫组化检测心脏组织TLR4、NF-κB p65、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达；HE、Masson和天狼星红染色观察心脏病理形态学变化。结果：与对照组比较，模型组小鼠心肌纤维数量明显减少，心肌组织排列紊乱，胶原纤维明显增多；血清FBG、CK-MB、IL-6、MCP-1、TNF-α、TG、LDL-C含量显著升高（P<0.01,P<0.05）,HDL-C水平显著降低（P<0.01）,TNF-α、IL-6、MCP-1显著升高（P<0.01）；心脏组织TLR4、NF-κB p65、Cleaved caspase-3、Cleaved PARP、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达显著增强（P<0.01,P<0.05）。与模型组比较，补阳还五汤干预后，DCM小鼠心脏病理损伤程度明显改善；血清CK-MB、IL-6、MCP-1、TNF-α、TG、LDL-C水平显著下降（P<0.01,P<0.05）,HDL-C水平显著上调（P<0.05）,TNF-α、IL-6、MCP-1显著降低（P<0.01,P<0.05）；心肌组织TLR4、NF-κB p65、Cleaved caspase-3、Cleaved PARP、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达显著降低（P<0.01,P<0.05）。结论：补阳还五汤可通过抑制TLR4/NF-κB通路及促凋亡因子表达，对DCM小鼠发挥抗炎和抗凋亡作用，减轻心脏病理损伤，从而发挥心脏保护作用。更多还原

【Abstract】 Objective: To explore the protective effect of Buyang Huanwu Decoction on myocardial tissue and the influence of inflammatory and apoptotic factors in mice with diabetes cardiomyopathy(DCM). Methods: A total of 30 db/db mice(7-8 weeks old) were raised for 10 weeks to develop DCM and randomly divided into model group, Buyang Huanwu Decoction group, and Shuluodite group, with 10 mice in each group. Another 10 db/m mice(7-8 weeks old) were included in the control group. Corresponding medication treatment were provided for 12 weeks, the levels of blood glucose(FBG), creatine kinase isoenzyme(CK-MB), interleukin-6(IL-6), monocyte chemokine 1(MCP-1), tumor necrosis factor-α(TNF-α), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were detected. The mRNA expression of Toll like receptor(TLR4) and nuclear transcription factor-κB p65(NF-κB p65) were detected by qRT-PCR. Western Blot was used to detect the expression of TLR4, NF-κB p65, Cleaved caspase-3 and Cleaved PARP in mouse cardiac tissue.Immunohistochemical was used to detect the expression of TLR4, NF-κB p65, I and II collagen in cardiac tissue. HE, Masson,and Sirius red staining were used to observe the pathological and morphological changes of the heart. Results: Compared with the control group, the model group mice showed a significant decrease in the number of myocardial fibers, disordered arrangement of myocardial tissue and a significant increase in collagen fibers, the contents of FBG, CK-MB, IL-6, MCP-1, TNF-α, TG,LDL-C were significantly increased(P<0.01, P<0.05), while the HDL-C levels was decreased(P<0.01), TNF-α, IL-6, and MCP-1 were significantly elevated(P<0.01), at the same time, the expression of TLR4, NF-κB p65, Cleaved caspase-3, Cleaved PARP, and I and II collagen proteins was significantly enhanced in cardiac tissue(P<0.01, P<0.05). Compared with the model group, after intervention with Buyang Huanwu Decoction, the degree of cardiac pathological damage was significantly improved in DCM mice, the levels of CK-MB, IL-6, MCP-1, TNF-α, TG, and LDL-C significantly decreased(P<0.01, P<0.05), while the levels of HDL-C were significantly upregulated(P<0.01), TNF-α, IL-6, and MCP-1 were decreased(P<0.01, P<0.05),the expression of TLR4, NF-κB p65, Cleaved caspase-3, Cleaved PARP, I and II collagen was significantly reduced(P<0.01,P<0.05). Conclusion: Buyang Huanwu Decoction can exert anti-inflammatory and anti-apoptotic effects on DCM mice by inhibiting the TLR4/NF-κB pathway and pro-apoptotic factor expression, reducing cardiac pathological damage, and thus exerting cardioprotective effects.更多还原