普萘洛尔调节SDF-1/CXCR4信号轴对自身免疫性心肌炎大鼠心肌细胞凋亡影响

    Effect of propranolol on myocardial cell apoptosis in rats with autoimmune myocardioptis by regulating the SDF-1/CXCR4 signaling axis

      摘要
    • 摘要:
      目的 探讨普萘洛尔(Pro)调节基质细胞衍生因子1(SDF-1)/趋化因子受体4(CXCR4)信号轴对自身免疫性心肌炎（AM）大鼠心肌细胞凋亡的影响。
      方法 取60只大鼠，随机选取12只设为空白组（CON组），其余48只用于构建AM大鼠模型。造模成功后，将模型大鼠随机分为AM模型组、Pro干预组、WZ811（SDF-1/CXCR4信号轴抑制剂）组、Pro+WZ811联合干预组，每组12只，各组均每日给药1次，连续干预2周。ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素-6（IL-6）水平；H&E染色观察心肌组织病理学变化；TUNEL法检测心肌组织细胞凋亡情况；Western blot检测BCL-2相关X蛋白（Bax）、B细胞淋巴瘤/白血病-2蛋白(Bcl-2)、裂解的半胱氨酸天冬氨酸蛋白酶3(cleaved Caspase‐3)以及SDF-1/CXCR4通路蛋白表达。
      结果 与CON组相比，AM组心肌组织结构异常，出现大面积坏死、水肿和炎性细胞浸润现象，心肌组织病理评分、IL-6、TNF-α含量、心肌细胞凋亡率、Bax、cleaved Caspase‐3蛋白水平显著增加（P<0.05），Bcl-2、SDF-1和CXCR4蛋白水平显著下调（P<0.05）；与AM组比较，Pro组心肌组织细胞坏死、水肿改善，炎性细胞浸润减少，心肌组织病理评分、IL-6、TNF-α含量、心肌细胞凋亡率、Bax、cleaved Caspase‐3蛋白水平显著降低（P<0.05），Bcl-2、SDF-1和CXCR4蛋白水平显著升高（P<0.05），而WZ811组大鼠以上指标呈现相反趋势；WZ811逆转了Pro对AM大鼠心肌细胞凋亡的改善效果。
      结论 Pro可能通过激活SDF-1/CXCR4信号通路减轻AM大鼠心肌细胞凋亡。

       

      Abstract:
      AIM To investigate the effect of propranolol (Pro) on myocardial cell apoptosis in rats with autoimmune myocardioptis (AM) by regulating the stromal cell-derived factor 1 (SDF-1)/chemokine receptor 4 (CXCR4) signal axis.
      METHODS Sixty rats were randomly selected and assigned to a blank group (n=12, CON group) and AM rat model was constructed in the rest of the rats. The rats with successfully constructed AM model were randomly grouped into AM group, Pro group, SDF-1/CXCR4 signal axis inhibitor (WZ811) group, and Pro+WZ811 group, with 12 rats in each group and received treatment once a day for 2 continuous weeks. ELISA method was applied to detect levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), H&E staining was applied to observe pathological changes in myocardial tissue, TUNEL method was applied to detect apoptosis in myocardial tissue and Western blot was applied to detect the expressions of BCL-2 associated X protein (Bax), B-cell lymphoma/leukemia 2 protein (Bcl-2), cleaved Caspase‐3, and SDF-1/CXCR4 pathway proteins.
      RESULTS Compared with those of the CON group, the myocardial tissue structure of the AM group showed abnormal, with extensive necrosis, edema and inflammatory cell infiltration, and the pathological score of myocardial tissue, contents of IL-6 and TNF-α, myocardial cell apoptosis rate and the expressions of Bax and cleaved Caspase-3 were increased (P<0.05) and the protein levels of Bcl-2, SDF-1 and CXCR4 were obviously down-regulated (P<0.05). Compared with those in the AM group, the necrosis and edema of myocardial tissue cells in Pro group improved, and inflammatory cell infiltration decreased, the pathological score of myocardial tissue, contents of IL-6 and TNF-α, myocardial cell apoptosis rate, and the protein levels of Bax and cleaved Caspase-3 were obviously reduced (P<0.05), and the protein levels of Bcl-2, SDF-1 and CXCR4 were obviously increased (P<0.05). All the above indicators in the WZ811 group showed an opposite trend and WZ811 reversed the improvement effect of propranolol on myocardial cell apoptosis in AM rats.
      CONCLUSION Propranolol alleviates myocardial cell apoptosis in AM rats by activating the SDF-1/CXCR4 signaling pathway.

       

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