| 赵滋苗,秦金燕,臧倩,程建超.黄连解毒汤靶向PINK1/Parkin通路调控线粒体自噬缓解脓毒症心肌损伤的机制研究[J].浙江中西医结合杂志,2025,35(10): |
| 黄连解毒汤靶向PINK1/Parkin通路调控线粒体自噬缓解脓毒症心肌损伤的机制研究 |
| To study the mechanism of Huanglian-Jiedu decoction targeting PINK1/Parkin pathway to regulate mitophagy in alleviating sepsis-induced myocardial injury |
| 投稿时间：2024-08-07 修订日期：2025-09-09 |
| DOI： |
| 中文关键词: 黄连解毒汤 脓毒症 心肌损伤 线粒体自噬 PINK1/Parkin |
| 英文关键词:Huanglian Jiedu decoction Sepsis Myocardial injury Mitophagy PINK1/Parkin |
| 基金项目:浙江省中医药科技计划项目(2024ZL076) |
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| 中文摘要: |
| 目的:探究黄连解毒汤缓解脓毒症诱导的心肌损伤的分子机制。方法:在体内通过盲肠结扎穿刺术构建脓毒症心肌损伤大鼠模型,并用黄连解毒汤加以处理。体外用LPS处理H9C2细胞构建细胞模型,并用含药血清进行处理。HE染色检测大鼠心肌组织的病理变化,并通过透射电镜观察线粒体形态变化。ELISA检测BNP、cTnI、TNF-α,IL-1β和IL-6 的变化,Western blot检测自噬水平以及PINK1/Parkin通路蛋白的变化。CCK-8和流式细胞术检测细胞的活力和凋亡水平。免疫荧光观察H9C2细胞线粒体中的自噬小体。结果:与假手术组相比,盲肠结扎穿刺术组大鼠的心肌组织有大量炎性细胞浸润,心肌细胞排列紊乱,线粒体完整性遭到破环,血清中的TNF-a、IL-1β和IL-6显著升高且BNP和c-TnI水平也显著上升,但线粒体自噬水平显著降低。经不同剂量(1.5g/kg?d和3g/kg?d)的黄连解毒汤治疗后,情况得到改善,且高剂量的荒凉解毒汤的效果最好。体外试验结果发现,与control组相比,LPS诱导的H9C2细胞中,线粒体自噬水平显著下降,PINK1/Parkin通路也被显著抑制,细胞损伤加重。经不同剂量的含药血清处理后,与LPS组相比,细胞损伤得到改善,线粒体自噬水平显著增强,PINK1/Parkin通路被激活。结论:黄连解毒汤通过上调PINK1/Parkin通路,增加线粒体自噬水平,进而缓解脓毒症心肌损伤。 |
| 英文摘要: |
| Objective: To investigate the molecular mechanism of Huanglian-Jiedu decoction in alleviating sepsis-induced myocardial injury.Methods: A rat model of sepsis-induced myocardial injury was established by cecal ligation and puncture and treated with Huanglian-Jiedu decoction. H9C2 cells were treated with LPS in vitro to construct a cell model and treated with drug-containing serum. The pathological changes of myocardial tissue were detected by HE staining, and the morphological changes of mitochondria were observed by transmission electron microscope. The levels of BNP, cTnI, TNF-α, IL-1β and IL-6 were detected by ELISA. The level of autophagy and PINK1/Parkin pathway proteins were detected by Western blot. CCK-8 and flow cytometry were used to detect the cell viability and apoptosis. Immunofluorescence was used to observe autophagosomes in the mitochondria of H9C2 cells.Results: Compared with the sham-operation group, the cecal ligation and puncture group showed a large number of inflammatory cell infiltration in the myocardial tissue, disordered arrangement of myocardial cells, and disruption of mitochondrial integrity. The serum levels of TNF-a, IL-1β, IL-6, BNP and c-TnI were also significantly increased, but the level of mitophagy was significantly decreased. After treatment with Huanglian Jiedu decoction at different doses (1.5g/kg?d and 3g/kg?d), the condition was improved, and the high-dose Huangliang Jiedu decoction had the best effect. In vitro experiments showed that compared with the control group, the level of mitophagy was significantly decreased, PINK1/Parkin pathway was also significantly inhibited, and cell damage was aggravated in H9C2 cells treated with LPS. After treatment with different doses of drug-containing serum, compared with LPS group, cell damage was ameliorated, the level of mitophagy was significantly enhanced, and PINK1/Parkin pathway was activated.Conclusions: Huanglian-Jiedu Decoction can alleviate sepsis-induced myocardial injury by up-regulating PINK1/Parkin pathway and increasing mitophagy. |
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