通冠胶囊对脓毒症大鼠心肌保护作用实验研究

Experimental Study of the Myocardial Protection on Septic Rats by Tongguan Capsule

目的探讨通冠胶囊对脓毒症大鼠心肌的保护作用。方法选择SD大鼠120只,行盲肠结扎穿孔术(CLP)复制脓毒症动物模型。造模后分为假手术组、模型组、通冠胶囊治疗组(治疗组),每组40只,每组按照不同时点分成5个亚组(CLP术后12h、24h、48h、72h及7天5个时点),每个亚组8只。模型组及治疗组均行盲肠结扎穿孔术,假手术组打开腹腔轻轻翻动盲肠后缝合腹壁切口,盲肠不作穿刺。模型组及假手术组给予生理盐水10mL/(kg·d)灌胃,治疗组给予通冠胶囊混悬液600mg/(kg·d)灌胃,每天1次,共7天。观察各组各时间点血流动力学变化左心室内压峰值(LVSP)、左心室等容收缩期压力最大变化速率(+dp/dtmax)、左心室舒张期压力下降最大变化速率(-dp/dtmax)、炎症因子肿瘤坏死因子(TNF-α)及白细胞介素-6(IL-6)、心肌损伤标记物肌钙蛋白-I(CTnI)。光镜及电镜下观察3天后各组大鼠心肌细胞形态变化。结果与假手术组比较,模型组术后24～72hLVSP、+dp/dtmax均降低,-dp/dtmax、CT-nI、TNF-α及IL-6均升高,差异均有统计学意义(P<0.01)。与模型组比较,治疗组24～72hLVSP、+dp/dt-max均升高,-dp/dtmax、CTnI、TNF-α及IL-6均降低,差异均有统计学意义(P<0.05,P<0.01)。光镜下显示治疗组心肌细胞偶见颗粒样变性,心肌横纹较清晰,冠状动脉扩张充血,间质轻度炎症。电镜下显示治疗组心肌细胞核结构完整,Z线较清晰,线粒体数目增加,可见肿胀,但嵴的结构较清晰,间质轻度纤维化。结论通冠胶囊可以改善脓毒症大鼠的心肌抑制状态,从而改善脓毒症的预后。

Objective To study the myocardial protection on septic rats by Tongguan Capsule （TC）. Methods Totally 120 SD rats were used to prepare the septic rat model using cecal, ligation and puncture （CLP）. After modeling they were divided into three groups, i. e., the sham-operation group, the model group, the treatment group （treated by TC）, 40 in each group. Each group was further divided into 5 subgroups accord- ing to different time points, i.e., 12 h, 24 h, 48 h, 72 h, and 7 days after CLP, 8 in each subgroup. CLP was performed in rats of the model group and the treatment group. The abdominal cavity of rats in the sham-operation group was opened. The incision of the abdominal wall was then sutured after their cecum was slightly flipped with- out puncture. Normal saline （at the daily dose of 10 mL/kg） was given by gastrogavage to rats in the model g＇roup and the sham-operation group. TC （at the daily dose of 600 mg/kg） was given to rats in the treatment group by gastrogavage, once daily, for 7 successive days. The hemodynamic changes such as left ventricular systolic pressure （LVSP）, left ventricular pressure maximal rate of fall （ -dp/dtmax）, left ventricular pressure maximal rate of rise （ ＋ dp/dtmax）, inflammatory factors E such as tumor necrosis factor-a （TNF-a） and, IL-6, troponin I （CTn I ） l were observed in all groups at each time point. The morphological changes of myocardial cells were observed under light and electron microscope 3 days later. Results Compared with the sham-opera- tion group, the LVSP and ＋dp/dtmax decreased, and- dp/dtmax, CTn ] , TNF-a, and IL-6 increased 24-72 h after surgery in the model group, showing statistical difference （P 〈0.01 ）. Compared with the model group, the LVSP and ＋ dp/dtmax increased, and -dp/dtmax, CTn I , TNF-a, and IL-6 decreased 24 -72 h after surgery in the treatment group, showing statistical difference （P 〈0.05, P 〈0.01 ）. Images under light microscope showed granular degeneration of myocardial cells could be occasionally seen in the treatment group. The transverse stria-tion of myocardial cells was quite clear. The coronary artery was dilated and congested, with mild inflammation of interstitium. Images under electron microscope showed that the nucleus of myocardial cells was complete with quite clear Z-line in the treatment group. The number of the mitochondria increased. The mitochondria was swol- len, but with more clear structure of cristae and mild fibrosis of interstitium. Conclusion TC could improve the de- pression state of myocardial cells of septic rats, thus improving the prognosis of sepsis.