| 引用本文:王继娟1，刘宏灿1，王维华2.水蛭素对高同型半胱氨酸大鼠血管平滑肌细胞的影响[J].世界中医药,2023,(10):. |
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| 水蛭素对高同型半胱氨酸大鼠血管平滑肌细胞的影响 |
| Hirudin Affects Vascular Smooth Muscle Cells in the Rat Model of Hyperhomocysteine |
| 投稿时间：2022-04-05 |
| DOI：10.3969/j.issn.1673-7202.2023.10.004 |
| 中文关键词: 水蛭素；血管平滑肌细胞；同型半胱氨酸；大鼠；血脂；胸主动脉组织；B细胞淋巴瘤-2 B细胞淋巴瘤-2相关X蛋白 胱天蛋白酶3；信号转导 |
| English Keywords:Hirudin Vascular smooth muscle cell Hyperhomocysteine Rat Blood lipid Thoracic aorta tissue B-cell lymphoma-2 Bcl-2-associated X protein(Bax) Cysteine aspartate-specific protease 3(caspase-3) Signal transduction |
| 基金项目:中国博士后科学基金面上资助项目（184698）；广东省中医药局科研项目(20201158) |
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| 中文摘要: |
| 目的：观察水蛭素对高同型半胱氨酸（Hcy）大鼠血管平滑肌细胞（VSMC）的作用机制。方法：50只SD大鼠，采用随机数字表法分为正常组、模型组和水蛭素3个不同剂量组（25、50、100 AT-U/mL），每组10只。正常组予以普通饲料喂养，模型组及水蛭素组大鼠予以普通饲料及DL-蛋氨酸灌胃，造模21周，测血脂4项、血清Hcy，水蛭素组皮下注射水蛭素，2周后测血脂和Hcy，取胸主动脉组织。采用苏木精-伊红（HE）染色和免疫组织化学染色观察胸主动脉组织病理变化及B细胞淋巴瘤-2（Bcl-2）、B细胞淋巴瘤-2相关X蛋白（Bax）和胱天蛋白酶3（Caspase3）表达；实时荧光定量（RT-qPCR）检测Bcl-2、Bax和Caspase3的mRNA表达。结果：水蛭素各剂量组三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）的含量显著降低（P<0.01），水蛭素高剂量组血清高密度脂蛋白胆固醇（HDL-C）的含量显著升高（P<0.01）；水蛭素各剂量组主动脉内膜增厚、VSMC增生减轻；水蛭素高、中剂量组胸主动脉组织Caspase3、Bax蛋白表达增多，Bcl-2蛋白的表达减少，水蛭素各剂量组Caspase3、Bax的mRNA不同程度降低，Bcl-2的mRNA表达显著降低（P<0.01），水蛭素高剂量组对胸主动脉组织Caspase3、Bcl-2、Bax的mRNA的调控最佳。结论：水蛭素可能通过调节脂质、促进Hcy诱导下异常增殖的VSMC凋亡，延缓动脉粥样硬化进展，而且可以通过Caspase3/Bax/Bcl-2凋亡信号通路有效促进高Hcy诱导的异常增殖的VSMC凋亡，为动脉粥样硬化的早期防治提供了新方向。 |
| English Summary: |
| To investigate the effect of hirudin on vascular smooth muscle cells(VSMCs) in the rat model of hyperhomocysteine(Hcy).Methods:Fifty SD rats were randomized into a normal group，a model group and low-，medium，and high-dose(25，50，and 100 AT-U/mL) hirudin groups according to the random number table method，with 10 rats in each group.The rats in the normal group were fed with an ordinary diet.The rats in the model group and hirudin groups were fed with an ordinary diet and administrated with DL-methionine by gavage.After 21 weeks，the serum levels of 4 lipid indicators and Hcy were measured.The rats in the hirudin group were subcutaneous injected with hirudin.Two weeks later，serum lipid and Hcy levels were measured and the thoracic aorta samples were collected.Hematoxylin-eosin staining and immunohistochemical staining were employed to observe the pathological changes of the thoracic aorta and determine the expression of B-cell lymphoma-2(Bcl-2)，Bcl-2-associated X protein(Bax)，and cysteine aspartate-specific protease 3(caspase-3).Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of Bcl-2，Bax，and caspase-3.Results:The hirudin groups had lower serum levels of triglyceride(TG)，total cholesterol(TC)，and low-density lipoprotein cholesterol(LDL-C)，and the high-dose hirudin group had higher serum level of high-density lipoprotein cholesterol(HDL-C)(P<0.01).The hirudin groups showed thickened aortic intima and mitigated VSMC hyperplasia.The medium- and high-dose hirudin up-regulated the protein levels of caspase-3 and Bax and down-regulated the protein level of Bcl-2 in the thoracic aorta tissue.The three doses of hirudin down-regulated the mRNA levels of Bcl-2(P<0.01)，caspase-3，and Bax，and the high-dose group demonstrated the strongest regulatory effect.Conclusion:Hirudin may delay the progression of atherosclerosis by regulating lipid metabolism and promoting the apoptosis of VSMCs with abnormal proliferation induced by Hcy.Moreover，hirudin may promote the apoptosis of VSMCs with abnormal proliferation induced by Hcy via the caspase-3/Bax/Bcl-2 signaling pathway.The study provides a new direction for the early prevention and treatment of atherosclerosis. |
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