神格散通过LOXL2/TGF-β1/IL-11信号通路抑制心肌梗死后心力衰竭大鼠心肌纤维化。

Q2 Medicine
Hang Xie, Boyong Qiu, Haitao Li, Ruoyu Shi
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引用次数: 0

摘要

目的:探讨神格散(SGP)对心肌梗死后心力衰竭大鼠心肌纤维化的影响及其与赖氨酸氧化酶样蛋白2 (LOXL2)/转化生长因子-β1 (TGF-β1)/IL-11信号通路的关系。方法:将72只SPF级雄性SD大鼠分为空白对照组、模型对照组、SGP小剂量组、SGP大剂量组、阳性对照组、SGP大剂量+LOXL2激活剂组,每组12只。除空白对照组外,其余各组心肌梗死后心力衰竭均由冠状动脉收缩引起。造模成功后立即给予相应处理,每天1次,连续4周。采用彩色多普勒超声检测大鼠左室缩短分数(LVFS)和左室射血分数(LVEF)。ELISA法测定血清中IL-1β、IL-6水平,Masson染色法测定心肌胶原体积分数(CVF)。免疫组化染色检测心肌组织中胶原Ⅰ和α-平滑肌肌动蛋白(α-SMA)的表达。采用qRT-PCR检测心肌组织中基质金属蛋白酶-9 (MMP-9)和金属蛋白酶组织抑制剂1 (TIMP-1) mRNA的表达。Western blotting检测心肌组织LOXL2、TGF-β1、IL-11蛋白的表达。结果:与空白对照组比较,模型对照组大鼠LVFS、LVEF降低,血清IL-6、IL-1β水平升高,CVF值升高,心肌组织胶原Ⅰ、α-SMA表达,MMP-9、TIMP-1 mRNA表达,LOXL2、TGF-β1、IL-11蛋白表达升高(PMMP-9、TIMP-1 mRNA表达均升高,LOXL2、TGF-β1、IL-11蛋白表达降低(p < 0.05)。神格散可能通过抑制LOXL2/TGF-β1/IL-11通路抑制心肌梗死后心力衰竭大鼠心肌纤维化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Shenge powder inhibits myocardial fibrosis in rats with post-myocardial infarction heart failure through LOXL2/TGF-β1/IL-11 signaling pathway.

Objectives: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway.

Methods: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for blank control group, post-myocardial infarction heart failure was induced by coronary constriction in all groups. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by Color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method, Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting.

Results: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, expressions of MMP-9 and TIMP-1 mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, the CVF value, the expressions of Collagen Ⅰ and α-SMA in myocardial tissue, expressions of MMP-9 and TIMP-1 mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins decreased (P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction.

Conclusions: Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.

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