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[竹节人参皂苷通过TGF-β1/Smad3信号通路抑制衰老大鼠心肌纤维化的作用]

[Effect of saponins extracted from Panax japonicas on inhibiting myocardial fibrosis by TGF-β1/Smad3 signaling pathway in aging rats].

作者信息

Song Ya-Nan, Wang Luo-Pei, Zheng Jie, Zhang Chang-Cheng, Wang Ting, Yuan Ding, Zhou Zhi-Yong

机构信息

Medical College of Three Gorges University, Yichang 443002, China.

Renhe Hospital of Three Gorges University, Yichang 443001, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2018 Nov;43(22):4513-4518. doi: 10.19540/j.cnki.cjcmm.20180724.006.

Abstract

To investigate the amelioration effect of saponins extracted from Panax japonicas (SPJ) on myocardial fibrosis in natural aging rats and its mechanisms, male SD rats aged 18 months were randomly divided into 3 groups (aging model group, low-dose SPJ group and high-dose SPJ group), with 10 rats in each group. SPJ groups were given SPJ at different doses (10, 60 mg·kg⁻¹·d⁻¹) consecutively for 6 months, meanwhile, aging model group was treated with the equal volume of saline for 6 months until 24 months old. Another 10 rats aged 6 month were used as young control group. The changes of myocardial morphological were observed by haematoxylin-eosin (HE) staining. Masson staining was used to observe the changes of collagen deposition in rat hearts. RT-PCR was used to detect the mRNA expression levels of myofibroblast marker α-SMA, collagen-related protein COL1α2, COL3α1 and matrix metalloproteinase MMP2, MMP9. Western blot was used to test the changes of the protein expressions of TGF-β1, p-Smad3, IL-1β and TNF-α in heart tissues. SPJ can effectively improve the arrangement of myocardial fibers, decrease inflammatory infiltration and reduce collagen deposition in aging rats. SPJ can effectively down-regulate the mRNA expression levels of COL1α2, COL3α1, α-SMA, MMP9, MMP2 and inhibit the protein expressions of TGF-β1, p-Smad3, TNF-α, IL-1β in the natural aging heart tissues. SPJ can effectively alleviate myocardial fibrosis in natural aging rats, and its mechanisms was related to the inhibition of the protein expressions of TGF-β1, p-Smad3 and the reduction of myocardial inflammation in rat hearts.

摘要

为探讨竹节人参总皂苷(SPJ)对自然衰老大鼠心肌纤维化的改善作用及其机制,将18月龄雄性SD大鼠随机分为3组(衰老模型组、SPJ低剂量组和SPJ高剂量组),每组10只。SPJ组大鼠分别给予不同剂量(10、60 mg·kg⁻¹·d⁻¹)的SPJ连续灌胃6个月,同时,衰老模型组给予等体积生理盐水灌胃6个月直至24月龄。另取10只6月龄大鼠作为青年对照组。采用苏木精-伊红(HE)染色观察心肌形态学变化。采用Masson染色观察大鼠心脏胶原沉积的变化。采用RT-PCR检测成肌纤维细胞标志物α-SMA、胶原相关蛋白COL1α2、COL3α1以及基质金属蛋白酶MMP2、MMP9的mRNA表达水平。采用蛋白质免疫印迹法检测心脏组织中TGF-β1、p-Smad3、IL-1β和TNF-α蛋白表达的变化。SPJ可有效改善衰老大鼠心肌纤维排列,减少炎症浸润,降低胶原沉积。SPJ可有效下调自然衰老心脏组织中COL1α2、COL3α1、α-SMA、MMP9、MMP2的mRNA表达水平,并抑制TGF-β1、p-Smad3、TNF-α、IL-1β的蛋白表达。SPJ可有效减轻自然衰老大鼠的心肌纤维化,其机制与抑制TGF-β1、p-Smad3蛋白表达以及减轻大鼠心脏炎症有关。

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