牛磺酸减轻内毒素诱导的大鼠心肌损伤

目的:探讨牛磺酸对内毒素(即脂多糖,LPS)诱导的大鼠心肌损伤的影响。方法:健康雄性Sprague-Dawley(SD)大鼠30只随机分为3组:正常对照组、内毒素模型组及牛磺酸处理组。正常对照组和内毒素模型组大鼠尾静脉注射生理盐水,牛磺酸处理组大鼠尾静脉注射牛磺酸(100 mg/kg),2 h后,内毒素模型组和牛磺酸处理组大鼠腹腔注射LPS(10 mg/kg),正常对照组大鼠腹腔注射生理盐水。注射内毒素6 h后,采集血样品和心肌组织,检测血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平;光镜下观察心肌形态学变化;Western blot检测心肌组织磷酸化核因子κB(p-NF-κB)、环氧合酶2(COX-2)、TNF-α、IL-6及血红素加氧酶1(HO-1)的表达。结果:与正常对照组比较,内毒素模型组大鼠血清SOD活性及心肌组织HO-1表达明显降低(P0.01),血清MDA、TNF-α和IL-6水平明显升高(P0.01),心肌组织p-NF-κB、COX-2、TNF-α及IL-6水平明显升高(P0.01)。与内毒素模型组比较,牛磺酸处理组大鼠血清MDA、TNF-α和IL-6水平明显降低(P0.01),牛磺酸处理明显降低心肌组织COX-2、TNF-α、IL-6及p-NF-κB水平(P0.01),血清SOD活性及心肌组织HO-1表达明显提高(P0.01)。组织学观察显示内毒素模型组大鼠心肌组织有炎症细胞浸润,心肌纤维排列疏松不规则,而正常对照组和牛磺酸处理组大鼠心肌纤维排列整齐规则。结论:牛磺酸预处理能减轻内毒素诱导的心肌损伤,其机制可能通过HO-1/CO信号下调p-NF-κB/COX-2而发挥作用。

Protective effects of taurine on LPS-induced myocardial damage in rats

AIM: To investigate the effects of taurine on lipopolysaccharide (LPS)-induced myocardial damage in rats. METHODS: Healthy male SD rats (n=30) were randomly divided into control group (CON), LPS model group (LPS) and taurine treatment group (TAU). The rats in CON group and LPS group were intravenously injected with normal saline, and the rats in TAU group were injected with taurine (100 mg/kg). After 2 h, the rats in LPS group and TAU group were intraperitoneally injected with LPS at 10 mg/kg, and the rats in CON group were injected with normal saline. Six hours after injection of LPS, the blood samples were collected for determination of superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. The myocardial tissues were processed for histological examination and the analysis of Western blot. RESULTS: Compared with CON group, LPS significantly reduced SOD activity in the serum and heme oxygenase 1 (HO-1) protein expression in the myocardial tissues, increased the serum content of MDA and levels of TNF-α and IL-6. LPS also significantly elevated the levels of TNF-α and IL-6, and up-regulated the cyclooxygenase-2 (COX-2) expression and phosphorylation of nuclear factor kappa B (NF-κB) in the myocardial tissues. Taurine pretreatment significantly elevated SOD activity and HO-1 protein expression level, decreased the levels of COX-2, TNF-α, IL-6 and phosphorylated NF-κB. Histological observation showed that taurine reduced inflammatory response in the myocardial tissue. CONCLUSION: Taurine attenuates LPS-induced myocardial damage in rats. The beneficial effects of taurine may be associated with its reduction of p-NF-κB/COX-2 signaling by activation of HO-1/CO.