牛黄中胆酸类成分改善大鼠脑缺血再灌注损伤及调节内质网应激作用比较  

Comparative study of cholic acid compounds of bezoar on anti-cerebral infarction and regulating endoplasmic reticulum stress

作　　者：徐晓琳[1] 马重阳[1] 王雪茜[1] 王国力[1] 翟昌明[1] 岳文超[1] 李长香[1] 张晓瑜[1] 沈晓东[1] 穆杰[1] 王庆国[1] 程发峰[1] 

机构地区：[1]北京中医药大学中医学院,北京100029

出　　处：《药物评价研究》2017年第1期11-19,共9页Drug Evaluation Research

基　　金：教育部博士点新教师基金项目(20130013120005)

摘　　要：目的观察牛黄中有效成分对大鼠脑缺血再灌注损伤的改善作用,从内质网应激角度探讨其作用机制,并对牛黄有效成分的药效进行比较研究。方法 SD大鼠随机分成6组:假手术组、模型组、清开灵(阳性药,3 m L/kg)组、牛磺酸(25mg/kg)组、熊去氧胆酸(UDCA,78 mg/kg)组、牛磺熊去氧胆酸(TUDCA,100 mg/kg)组,每组10只。制备大脑中动脉闭塞模型,造成大鼠脑缺血再灌注损伤,采用神经功能评分法评定神经功能缺损,TTC染色法测定脑梗死体积,免疫组化、Western blotting法检测缺血脑组织中内质网应激相关蛋白(P-PERK、P-EIF2α、ATF4)的表达情况。结果与假手术组比较,模型组大鼠神经功能评分显著降低(P<0.01);与模型组比较,清开灵组、UDCA组、TUDCA组神经功能评分显著升高(P<0.05、0.01)。与假手术组比较,模型组大鼠形成明显缺血灶(P<0.01);与模型组比较,各给药组均能明显减小脑梗死体积(P<0.01)。与假手术组比较,模型组海马区和皮层区的P-PERK、P-EIF2α、ATF4的表达明显升高(P<0.01);与模型组比较,各给药组均不同程度的减少了P-PERK、P-EIF2α、ATF4的表达,尤以清开灵、TUDCA的下降最明显。结论牛黄有效成分通过抑制内质网应激改善大鼠脑缺血再灌注损伤,其中TUDCA的作用优于牛磺酸和UDCA。Objective Using middle cerebral artery occlusion （MCAO） model to observe protective effect of effective components of bezoar on brain damage. To discuss the anti-cerebral ischemla mechanism and compare the efficacy of effective components of bezoar from the endoplasmic reticulum stress intervention angle. Methods Rats were stratified randomly divided into sham group, model group, Qingkailing group （positive drug, 3 mL/kg）, taurine group, ursodeoxycholic acid （UDCA, 78 mg/kg） group, taurine-conjugated ursodeoxycholic acid （TUDCA, 100 mg/kg） group. Through establish MCAO model in rats, observed the scores of the neurologic impairment, measured infarct volume by TTC. Immunohistochemistry and Western blotting were Used to detect the content of P-PERK, P-EIF2α, and ATF4. Results Compared with sham group, neurologic impairment scores of model group significantly reduced （P 〈 0.01）. Compared with model group, Qingkailing group, UDCA group, and TUDCA group significantly improved neurological function in rats （P 〈 0.05, 0.01）. Compared model group, all the treatment groups could significantly reduce the volume of cerebral infarction （P 〈 0.01）. Compared with sham group, expression of P-PERK, P-EIF2α, and ATF4 was significantly increased （P 〈 0.01）. Compared with model group, all the treatment groups reduced the expression of P-PERK, P-EIF2α, and ATF4 in varying degrees, effect of Qingkailing and TUDCA were more obvious. Conclusion The effective components ofbezoar alleviate cerebral ischernia reperfusion injury in rats by inhibiting endoplasmic reticulum stress, the effect of TUDCA is better than that oftaurine and UDCA.

关 键 词：内质网应激 脑缺血再灌注损伤 牛磺熊去氧胆酸 清开灵 牛磺酸 熊去氧胆酸 

分 类 号：R965[医药卫生—药理学]