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补阳还五汤对病毒性心肌炎模型小鼠心肌组织中MMPs和TIMPs表达的影响
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| 篇名： | 补阳还五汤对病毒性心肌炎模型小鼠心肌组织中MMPs和TIMPs表达的影响 |
| TITLE： | |
| 摘要： | 目的：探讨补阳还五汤对病毒性心肌炎（VMC）模型小鼠心肌组织中基质金属酶（MMPs）、组织金属蛋白酶抑制因子（TIMPs）表达的影响。方法：将雄性BALb/c小鼠随机分为对照组、模型组、阳性对照组[卡托普利，100 mg/（kg·d）]和补阳还五汤低、中、高剂量组[6、18、36 g/（kg·d）]，每组24只。除对照组外，其余各组小鼠均单次腹腔注射柯萨奇B3病毒以复制VMC模型。造模成功后，对照组和模型组小鼠均灌胃等容生理盐水，各给药组小鼠均灌胃相应药物，每日1次，连续30 d。观察各组小鼠的一般情况。以病毒接种当日为0 d，分别于4、10、20、30 d时检测小鼠心脏质量与体质量比值（HW/BW）；采用苏木精-伊红染色法观察小鼠心肌组织形态学特征，并进行心肌病理组织学评分；采用苦味酸天狼猩红染色法观察小鼠心肌组织中Ⅰ、Ⅲ型胶原蛋白的分布情况，并计算Ⅰ/Ⅲ型胶原蛋白比值。于30 d时，采用Western blotting法检测小鼠心肌组织中MMP-1、MMP-3、MMP-9、TIMP-1的相对表达量，并计算MMPs/TIMPs。结果：与对照组比较，模型组小鼠出现烦躁、拱背、对刺激反应减轻、体质量减轻甚至精神萎靡等症状；其心肌组织可见典型的炎症性改变和局部间质细胞充血，并伴有大量淋巴细胞浸润和Ⅰ、Ⅲ型胶原蛋白分布，其HW/BW（10～30 d各时间点）、心肌病理组织学评分（4～30 d各时间点）、Ⅰ/Ⅲ型胶原蛋白比值（4～30 d各时间点）以及MMP-1、MMP-9的相对表达量和MMPs/TIMPs均显著升高，而MMP-3、TIMP-1的相对表达量均显著降低（P＜0.05）。与模型组比较，各给药组小鼠上述症状均有不同程度改善，其HW/BW[各给药组10～30 d各时间点（补阳还五汤低剂量组10 d除外）]、心肌病理组织学评分（各给药组10～30 d各时间点）、Ⅰ/Ⅲ型胶原蛋白比值（阳性对照组和补阳还五汤高剂量组4～10 d各时间点和补阳还五汤低、中剂量组20～30 d各时间点）以及MMP-1（阳性对照组和补阳还五汤高剂量组）、MMP-9（各给药组）的相对表达量和MMPs/TIMPs（各给药组）均显著降低，而MMP-3（阳性对照组和补阳还五汤低、高剂量组）、TIMP-1（各给药组）的相对表达量均显著升高（P＜0.05）。结论：补阳还五汤可通过抑制心肌胶原蛋白增生，调节MMPs、TIMPs的表达，改善心肌MMPs/TIMPs的失平衡状态等途径来发挥对VMC模型小鼠心肌纤维化的抑制作用。 |
| ABSTRACT： | OBJECTIVE： To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis （VMC） model mice. METHODS： Male BALb/c mice were randomly divided into control group， model group， positive control group [captopril， 100 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6， 18， 36 g/（kg·d）]， with 24 mice in each group. Except for control group， other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling， control group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d， heart mass to body mass ratio （HW/BW） was measured at 4， 10， 20， 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining， and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining， and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d， relative expressions of MMP-1， MMP-3， MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay， and the ratio of MMPs to TIMPs was calculated. RESULTS： Compared with control group， mice in model group suffered from irritability， arch back， alleviation of stimulation response， reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium， accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW （at different time points of 10-30 d）， myocardial histopathological score （at different time points of 4-30 d）， ratio of type Ⅰ and Ⅲ collagen （at different time points of 4-30 d）， the expression of MMP-1 and MMP-9， ratio of MMPs to TIMPs were increased significantly， while the expression of MMP-3 and TIMP-1 were decreased significantly （P＜0.05）. Compared with model group， above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups （except for 10 d in Buyang huanwu decoction low-dose group）]， myocardial histopathological score （at different time points of 10-30 d in administration groups）， ratio of type Ⅰand Ⅲ collagen （at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group， at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups）， the expression of MMP-1 （positive control group and Buyang huanwu decoction high-dose group） and MMP-9 （administration groups）， ratio of MMPs to TIMPs （administration groups） were decreased significantly， while the expression of MMP-3 （positive control group， Buyang huanwu decoction low-dose and high-dose groups） and TIMP-1 （administration groups） were increased significantly （P＜0.05）. CONCLUSIONS： Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia， regulating the expression of MMPs and TIMPs， improving MMPs/TIMPs imbalance. |
| 期刊： | 2019年第30卷第22期 |
| 作者： | 秦又发，周光辉，潘春予，朱永坤，杨宇峰，蒲荣 |
| AUTHORS： | QIN Youfa，ZHOU Guanghui，PAN Chunyu，ZHU Yongkun，YANG Yufeng，PU Rong |
| 关键字： | 补阳还五汤；病毒性心肌炎；心肌纤维化；基质金属蛋白酶；组织金属蛋白酶抑制因子；小鼠 |
| KEYWORDS： | Buyang huanwu decoction； Viral myocarditis； Myocardial fibrosis； MMP；TIMP； Mice |
| 阅读数： | 168 次 |
| 本月下载数： | 5 次 |
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