目的 探討強心湯調(diào)控p32/OMA1/OPA1通路介導的線粒體功能防治慢性心力衰竭纖維化的作用機制。方法 除7只對照組小鼠外，余33只小鼠通過結(jié)扎冠狀動脈建立慢性心力衰竭小鼠模型，并將存活的28只小鼠隨機分為模型組、沙庫巴曲纈沙坦（陽性藥，15.17 mg·kg^-1）組及強心湯低、高劑量（21.69、43.38 g·kg^-1）組，每組7只，對照組、模型組給予等量純凈水，造模后每天ig給藥1次，連續(xù)4周。進行蘇木素-伊紅（HE）、Masson染色觀察各組小鼠心肌組織病理損傷和纖維化情況；透射電鏡觀察線粒體損傷情況；免疫組化法和Western blotting法檢測心臟組織中補體成分1q結(jié)合蛋白（p32）、線粒體內(nèi)膜蛋白1（OMA1）、視神經(jīng)萎縮蛋白1（OPA1）的表達情況；生化檢測法測定各組小鼠血清中三磷酸腺苷（ATP）含量。結(jié)果 與對照組比較，模型組小鼠心肌組織損傷嚴重、心肌纖維化，線粒體碎裂、嵴消失；p32、長鏈OPA1（L-OPA1）蛋白表達顯著降低（P＜0.01），OMA1、短鏈OPA1（S-OPA1）蛋白表達顯著升高（P＜0.01），血清ATP濃度水平顯著降低（P＜0.01）。與模型組比較，強心湯高劑量組小鼠心肌組織整齊、纖維化明顯改善，p32、L-OPA1蛋白表達顯著增加（P＜0.01），OMA1、S-OPA1蛋白表達顯著降低（P＜0.01），血清ATP含量明顯增加（P＜0.01）。結(jié)論 強心湯能夠積極調(diào)控p32/OMA1/OPA1通路發(fā)揮維持線粒體供能、減輕慢性心力衰竭模型小鼠心肌損傷和組織纖維化的作用。

Objective To investigate the mechanism of effects of Qiangxin Decoction in modulating p32/OMA1/OPA1 pathway-mediated mitochondrial function against fibrosis in heart failure. Methods Except for seven mice in the control group, the remaining 33 mice established a mouse model of chronic heart failure by ligating the coronary artery, and the 28 surviving mice were randomly divided into model group, Qiangxin Decoction low and high dose (21.69 and 43.38 g·kg^-1) group, and sacubitril valsartan (positive drug, 15.17 mg·kg^-1) group, with seven mice in each group. After modeling, the mice in each group were treated with ig drugs once a day for four consecutive weeks, in control group and model group were given by equal volume of pure water. HE and Masson staining were performed to observe the pathological injury and fibrosis of myocardial tissue in each group. The mitochondrial damage was observed by transmission electron microscope. The expression of p32, OMA1 and OPA1 proteins in cardiac tissues was detected by immunohistochemistry and Western blotting. The content of ATP in serum was determined by biochemical detection. Results Compared with the control group, the model group exhibited severe myocardial damage, fibrosis, mitochondrial fragmentation, and cristae loss, protein expression of p32 and L-OPA1 was reduced (P < 0.01), while that of OMA1 and S-OPA1 was elevated (P < 0.01), and serum ATP concentration was significantly lower (P < 0.01). In comparison to the model group, the myocardial tissue of mice in Qiangxin Decoction high dose groups was well-organized, with significant improvement in fibrosis, protein expression of p32 and L-OPA1 increased (P < 0.01), while that of OMA1 and S-OPA1 decreased (P < 0.01), and serum ATP levels were significantly elevated (P < 0.01). Conclusion Qiangxin Decoction can actively regulate the p32/OMA1/OPA1 pathway, thereby playing a role in maintaining mitochondrial energy supply, and reducing myocardial injury and tissue fibrosis in CHF model mice.

R285.5

國家自然科學基金地區(qū)基金（82160887）；廣西自然科學基金項目（2021GXNSFAA220111）；廣西岐黃學者培養(yǎng)項目（NO.2022015-003-02）；國家中醫(yī)藥傳承創(chuàng)新中心項目（2023019-10）；廣西中醫(yī)藥大學研究生教育創(chuàng)新計劃項目（YCBXJ2023024）