参葛散通过LOXL2/TGF-β1/IL-11信号通路抑制心肌梗死后心力衰竭大鼠的心肌纤维化
[Shenge powder inhibits myocardial fibrosis in rats with post-myocardial infarction heart failure through LOXL2/TGF-β1/IL-11 signaling pathway].
作者信息
Xie Hang, Qiu Boyong, Li Haitao, Shi Ruoyu
机构信息
Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou 450053, China.
Heart Center, the First Affiliated Hospital of Henan University of Chinese Medicine,National Regional Traditional Chinese Medicine (Cardiovascular) Diagnosis and Treatment Center, Zhengzhou 450099, China.
出版信息
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2025 May 25;54(3):350-359. doi: 10.3724/zdxbyxb-2024-0606.
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 the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. 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, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, - and - mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all <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, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, - and - mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all <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.
目的
探讨参葛散（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酰氧化酶样蛋白2（LOXL2）/转化生长因子-β1（TGF-β1）/白细胞介素-11（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，采用冠状动脉缩窄法制备心肌梗死后心力衰竭模型。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心动图检测大鼠左心室短轴缩短率（LVFS）和左心室射血分数（LVEF）。采用酶联免疫吸附测定（ELISA）法分析血清白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平。采用Masson染色法评估心肌胶原容积分数（CVF）。采用免疫组织化学染色法检测心肌组织中Ⅰ型胶原和α-平滑肌肌动蛋白（α-SMA）的表达。采用实时荧光定量聚合酶链反应（qRT-PCR）检测心肌组织中基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制因子1（TIMP-1）的mRNA表达。采用蛋白质免疫印迹法检测心肌组织中LOXL2、TGF-β1和IL-11蛋白的表达。
结果
与空白对照组比较，模型对照组LVFS和LVEF降低，血清IL-6和IL-1β水平升高，CVF值、心肌组织中Ⅰ型胶原和α-SMA的表达、MMP-9和TIMP-1的mRNA及LOXL2、TGF-β1、IL-11蛋白表达均增加（均P<0.05）。与模型对照组比较，SGP小剂量组、SGP大剂量组和阳性对照组LVFS和LVEF升高，血清IL-6和IL-1β水平降低，CVF值、心肌组织中Ⅰ型胶原和α-SMA的表达、MMP-9和TIMP-1的mRNA及LOXL2、TGF-β1、IL-11蛋白表达均降低（均P<0.05）；而LOXL2激活剂可逆转高剂量SGP对心肌梗死后心力衰竭大鼠心肌纤维化的改善作用。
结论
参葛散可能通过抑制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。
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