心脉隆对缺氧缺血性脑损伤模型新生大鼠心肌细胞凋亡的影响

目的研究心脉隆（Xinmailong,XML）对缺氧缺血性脑损伤（HIBD）模型新生大鼠心肌细胞凋亡的影响。方法 96只新生7日龄SD大鼠采用随机数字表法分为3组,每组32只：假手术对照组（Sham组）、HIBD模型对照组（HIBD组）、HIBD＋XML组（XML组）。结扎实验鼠左颈总动脉后吸入8%O22.5 h制成HIBD模型,XML组在模型建立后,空气复苏5 min并立即给予XML注射液5 mg·kg^-1腹腔注射,其余2组接受同剂量的生理盐水。各组于缺氧缺血（HI）后24 h、48 h、72 h、7 d 4个时间点（每个时间点各8只）分批取心肌组织,HE染色后光镜下观察心肌组织病理形态学改变;Hoechst33258荧光染色及原位末端标记法（TUNEL）定性和定量检测心肌细胞凋亡。结果 Sham组死亡0只;HIBD组死亡4只;XML组死亡2只,各组间存活率差异无统计学意义（P〉0.05）。Sham组各时间点心肌组织均仅见散在的凋亡细胞,而HIBD组及XML组心肌细胞凋亡指数均于HI后24 h即开始升高,72 h达到高峰,之后逐渐下降,持续至7 d仍显著高于Sham组（P〈0.05）;XML组与HIBD组相比上述指标显著降低（P〈0.05）。结论新生大鼠HIBD后早期心肌细胞即可出现明显凋亡,以HI后72 h更明显;XML能够明显抑制HIBD模型新生大鼠心肌细胞凋亡的发生,发挥对缺氧损伤心肌细胞的保护作用。

The Effect of Xinmailong on Apoptosis of Myocardial Cells in Neonatal Rat Hypoxic-ischemia Brain Damage Model

Objective To investigate the effect of Xinmailong（XML） on apoptosis of myocardial cells in neonatal rat hypoxic-ischemia brain damage（HIBD） model.Methods A tolal of 96 7-day-old Sprague-Dawley（SD） rats were divided into 3 groups by random number table method（n=32 in each group）：sham operated control group（Sham group）、hypoxic-ischemia brain damage model control group（HIBD group）、HIBD＋XML group（XML group）.The HIBD model was made by ligating the left common carotid artery followed by an hypoxic（8% oxygen） episode of 2.5 hours duration.XML injection（5 mg·kg^-1） was injected intraperitoneally into those rats in XML group immediately after the animal model of HIBD was established and treated with room-air resuscitation for five minutes.While equal dose physiological saline was given to the rats of other two groups.The myocardial tissue samples were obtained in batches at four time points of 24 h,48 h,72 h,7 d after hypoxic-ischemia（HI）（eight rats at each time point）.The pathological changes of myocardium were observed by HE staining under optical microscope;Myocardial cells apoptosis were investigated both qualitatively and quantitatively by fluorescence staining of hoechst33258 and deoxynucleotidyl transfease-mediated d-UTP nick end labeling（TUNEL） method.Results All rats survived in Sham group,and four rats died in HIBD group while only two died in XML group;Comparison of surviral rates among the three different groups showed no statistical difference（P〈0.05）.There were only sporadic apoptotic cells in Sham group at each time point.While both the levels of cadiocyte apoptotic indexes（AI） in HIBD and XML groups began to increase at 24 h after HI,reached a peak at 72 h and then gradually decreased till the 7th day but still higher than that in Sham group（P〈0.05）;The above-mentioned index in XML group was significantly lower than that in HIBD group（P〈0.05）.Conclusion In neonatal rat HIBD model,myocardial tissue was subjected to obvious apoptosis at the early stage after HI,especially at the time point of 72 h.The medicine XML could exert protective effects on hypoxia-induced myocardial injury by inhibiting apoptosis of myocardial cells in HIBD model.