天麻素对脑缺血致心肌损伤及NGF/TrkA表达的影响

Effect of gastrodin on myocardial injury caused by cerebral ischemia and the expression of NGF/TrkA

目的观察天麻素对脑缺血致心肌损伤大鼠的治疗效果及神经生长因子(NGF)/酪氨酸激酶受体A(TrkA)的表达影响,探讨天麻素对心脏的保护机制。方法将40只雄性SD大鼠随机分为正常组、假手术组、模型组和天麻素组,每组10只。模型组和天麻素组均采用栓塞大脑中动脉法(MCAO)制备右侧局灶性脑缺血大鼠模型,天麻素组通过腹腔注射天麻素注射液[10 mg/(kg·d-1)],干预14 d。干预结束后,大鼠心肌组织病理学变化采用HE染色法检测,动脉血清中炎性因子包括肿瘤坏死因子-α(TNF-α)和白细胞介素10(IL-10)的含量采用酶联免疫吸附法(ELISA)检测,心肌组织中NGF、TrkA的表达采用免疫组织化学染色法(IHC)和蛋白免疫印迹法(WB)检测。结果与正常组和假手术组相比,模型组大鼠心肌纤维断裂明显,有大量炎性细胞浸润;动脉血清中促炎细胞因子TNF-α浓度明显升高(P<0.01);大鼠心肌组织中NGF和TrkA的蛋白表达升高(P<0.05)。与模型组相比,天麻素组大鼠心肌纤维损伤有所改善,炎性细胞浸润减少;动脉血清中促炎细胞因子TNF-α的浓度显著降低(P<0.01),抗炎细胞因子IL-10的浓度显著升高(P<0.01);大鼠心肌组织中NGF(P<0.05)和TrkA(P<0.01)的蛋白表达明显升高。结论脑缺血可使大鼠心肌组织出现炎症性损伤,NGF/TrkA可能参与调节机体炎症反应过程;天麻素可能通过上调NGF/TrkA、降低TNF-α、升高IL-10来减轻脑缺血大鼠所致的心肌损伤。

Objective To observe the therapeutic effect of gastrodin on myocardial injury induced by cerebral ischemia and on the expression of nerve growth factor(NGF)/tyrosine kinase receptor A(TrkA)in rats,so as to explore the protective mechanism of gastrodin on the heart.Methods Forty male SD rats were randomly divided into the normal group,the sham-operation group,the model group and the gastrodin group,with 10 rats in each group.The rat model of right focal cerebral ischemia was established by middle cerebral artery occlusion(MCAO)in the model group and the gastrodin group.In the gastrodin group,the rats were intraperitoneally injected with gastrodin injection[10 mg/(kg·d-1)]for 14 days.After intervention,HE staining was adopted to detect the histopathological changes of rat myocardium.Enzyma-linked immunosorbent assay(ELISA)was employed to determine the contents of inflammatory factors including tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in arterial serum.The expressions of NGF and TrkA in myocardial tissue were detected by immunohistochemical staining(IHC)and Western blot(WB).Results Compared with the normal group and the sham-operation group,the model group had obvious myocardial fiber fracture,abundant inflammatory cell infiltration,as well as significantly increased concentration of pro-inflammatory cytokines TNF-αin arterial serum(P<0.01).They also had significantly increased protein expressions of NGF and TrkA in the myocardial tissue of rats(P<0.05).Compared with the model group,the gastrodin group had improved myocardial fiber fracture and reduced inflammatory cell infiltration,but significantly decreased the concentration of pro-inflammatory cytokine TNF-αin arterial serum(P<0.01).They had significantly increased concentration of anti-inflammatory cytokine IL-10(P<0.01),and significantly increased protein expressions of NGF(P<0.05)and TrkA(P<0.01)in the myocardial tissue of rats.Conclusion Cerebral ischemia can cause inflammatory damage in rat myocardia,and NGF/TrkA may be involved in regulating the inflammatory response.Gastrodin may alleviate myocardial injury induced by cerebral ischemia by means of up-regulating NGF/TrkA,decreasing TNF-αand increasing IL-10.