甲硫氨酸维B_1与丹参酮ⅡA磺酸钠对梗阻性黄疸大鼠内毒素血症影响及心肌保护的实验研究

Effects of Methionine and Vitamin B_1 and Sodium Tanshinone ⅡA Sulfonate on Endotoxemia and Myocardial Protection in Rats with Obstructive Jaundice

目的探讨梗阻性黄疸(OJ)大鼠血浆内毒素(ET)、TNF-α、CK-MB、心肌丙二醛(MDA)、超氧化物歧化酶(SOD)水平变化及甲硫氨酸维B1(MVB1)与丹参酮ⅡA磺酸钠(STS)对上述检测因子变化的影响及意义。方法以大鼠胆总管结扎(BDL)为OJ模型,随机分为实验对照(EC)组、MVB1组、STS组及MVB1与STS联合(M-S)组,设立假手术组(sham,n=5),BDL后1～13 d予大鼠腹腔内注射相应剂量药物,采用放射免疫法测定BDL后2,6,10,14 d血浆ET、TNF-α、CK-MB及14 d心肌组织MDA、SOD水平并观察大鼠死亡率与心肌组织病理学改变。结果 BDL后大鼠死亡率为10%;BDL大鼠血浆ET、TNF-α、CK-MB水平与心肌组织MDA进行性升高,SOD水平显著下降(P<0.001);与EC组比较,STS、MVB1与M-S组血浆ET、TNF-α、CK-MB与心肌MDA水平下降,SOD水平升高,其差异有统计学意义,M-S组对上述指标影响较STS、MVB1显著(P<0.001);与MVB1组比较,STS对ET、CK-MB、MDA、SOD水平影响差异显著,对TNF-α水平无明显差异(P>0.05)。光镜下:EC组心肌细胞水肿,心肌纤维排列混乱,颗粒状坏死,心肌与心外膜毛细血管充血,少量炎细胞浸润;MVB1组、STS组上述病理变化程度较轻,M-S组心肌细胞轻度混浊,无明显坏死,少见炎细胞渗出。结论 ETM、TNF-α与心肌组织MDA水平进行性升高及SOD水平显著下降是OJ时大鼠心肌组织损害的重要因素之一。MVB1与STS对OJ大鼠血浆ET、TNF-α有抑制作用,STS可明显改善OJ时心肌组织氧自由基损害,STS与MVB1联合运用,表现出更有效的抗内毒素血症与生物膜脂质过氧化作用,发挥保护重要脏器的功能。

Objective To research the changes of endotoxin（ET） ,TNF -a,CK -MB in plasma and myocardial superoxide dismutase （SOD） and malondialdehyde （MDA） of rats with obstructive jaundice（OJ） and effects of sodium tanshinone IIA sulfonate （STS） and methionine and vitamin B1 （ MVB1 ） on the changes. Methods OJ rats were randomly divided into experimental control group（ EC group,n = 20） , MVB1 group （n = 20） ,STS group（ n=20） and combined group with MVB1 and STS（ M -S group, n = 20 ）. From the 1st to 13th day after operation EC, MVB1 and STS groups were respectively injected with equal volume of isotonic sodium chloride,MVB1 and STS. M - S group received MVB1 and STS together. Levels of ET,TNF -a and CK - MB in plasma on the days 2nd, 6th, lOth and 14nd after operation and myocardial MDA, SOD on the day 14th were respectively determined with radioimmunoassay. Meanwhile, the histopathological changes of myocardial tissue and mortality rate of rats were observed. Results The mortality rate of rats with OJ was 10%. In the groups after BDL,levels of ET,TNF -a , CK - MB in plasma and MDA in myocardial tissue were rapidly elevated and myocardial SOD decreased（ P 〈0. 001 ）. Compared with EC group,levels of plas- mic ET,TNF -a , CK -MB and myocardial MDA were declined and myocardial SOD levels was increased in STS, MVB1 and M - S groups. There had statistical difference in the changes. Compared respectively with STS and MVB1 groups ,level changes of the above tested cytokines in M - S group were significant（ P 〈 0. 001 ）. There had statistical difference in the level changes of ET, CK -MB,MDA and SOD between MVB1 and STS groups,no statistical difference in TNF-a changes. Under the light microscope, histological examination in EC group showed swelling and granular condensation and dissolution of some myocardial fibers. Sub - epicardial and myocardial capillaries showed mild congestion. A few inflammatory cells infiltration was observed in the myocardium and epicardium. The histological changes were mild in MVB1 and STS groups. The changes had significant difference between EC group and M - S group. Conclusion That elevation of TNF - a and ET levels in plasma and myocardial MDA content and the decrease of SOD ananty may be one of the most important factors of myocadial injury of rats with obstructive jaundice. MVB1 and STS can restrain the increase of plasmic TNF - a and ET of rats and protect myocardial tissue of OJ rats .