茯苓四逆汤对脓毒症大鼠心肌保护机制的研究

Study on Myocardial Protection Mechanism of Fuling Sini Decoction on Sepsis Rats

目的研究茯苓四逆汤对脓毒症大鼠心肌抑制的保护作用机制。方法取SPF级SD雄性大鼠100只,随机分成5组:假手术组、脓毒症组,茯苓四逆汤低剂、中、高剂量组(1.3 g/d、2.6 g/d、3.9 g/d)。假手术组、脓毒症组给予等容量0.9%氯化钠注射液,茯苓四逆汤各剂量组给予相应药物,均为灌胃给药;盲肠结扎穿孔法制作脓毒症模型,假手术组仅是暴露盲肠,造模后6 h开始给药,每日剂量分2次给药,直至造模后第3日,记录其生存状态,并在术前、术后24 h、48 h、72 h 3个时间点各选5只大鼠尾静脉取血并处死,取心肌组织后超低温保存备用,测定肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、心型脂肪酸结合蛋白(HFABP)水平。结果脓毒症组及中药各剂量组的大鼠TNF-α、IL-6、H-FABP明显升高,与假手术组差异有统计学意义(P <0.01);与脓毒症组同时间点比较,中药各剂量组的大鼠TNF-α、IL-6水平明显下降(P <0.01),H-FABP水平也明显下降(P <0.05);而中药各剂量组同时间比较发现,剂量越高,其TNF-α、IL-6水平下降越明显(P <0.01或P <0.05);不同剂量治疗组中比较发现,随着时间的延长,剂量越高的茯苓四逆汤对于改善H-FABP水平越好(P <0.05)。结论茯苓四逆汤对脓毒症大鼠心肌抑制具有良好保护作用,其机制可能与减少炎症释放有关。

Objective: To investigate the myocardial protection mechanism of Fuling Sini Decoction(FLSND) on sepsis rats. Methods: 100 rats were randomly divided into 5 groups: sham operation group,sepsis group,FLSND low dose,medium and high dose groups(1.3 g/d,2.6 g/d,3.9 g/d). Sham operation group and sepsis group were given normal saline of equal volume,and FLSND groups were given corresponding drugs by intragastric administration. Cecum ligation and puncture were used to make sepsis model. Sham operation group only exposed the cecum. The drug was administered six hours after the model was made. The survival status of the rats was recorded. The rats were killed after 24 h,48 h and 72 h,and the levels of TNF-α,IL-6 and H-FABP were detected. Results: TNF-α,IL-6 and H-FABP in sepsis group and FLSND groups were significantly higher than those in sham operation group(P < 0.01). Compared with the sepsis group at the same time point,the levels of TNF-α and IL-6 decreased significantly in each dose group(P < 0.01),as well as the levels of H-FABP(P < 0.05). In FLSND groups,the higher the dosage,the lower the levels of TNF-a and IL-6(P < 0.01,vs low-dose group,P < 0.05,vs medium-dose group). With the prolongation of time,the higher the dosage of Fuling Sini Decoction,the better the improvement of H-FABP level(P < 0.05). Conclusion: Fuling Sini Decoction has a good protective effect on myocardial inhibition in sepsis rats,which may be related to the reduction of inflammatory release.