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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 To observe the effect of the active ingredients of Bezoar on the improvement of cerebral ischemia-reperfusion injury in rats and its mechanism of action from the perspective of endoplasmic reticulum stress. The pharmacodynamic effects of the active ingredients of Bezoar were compared. Methods SD rats were randomly divided into 6 groups: sham operation group, model group, Qingkailing (positive drug, 3 m L / kg), taurine (25 mg / mg / kg), and tauroursodeoxycholic acid (TUDCA, 100 mg / kg). The middle cerebral artery occlusion model was established to induce cerebral ischemia-reperfusion injury in rats. Neurological deficits were assessed by neurological function score. The volume of cerebral infarction was measured by TTC staining. Immunohistochemistry and Western blotting were used to detect the endoplasmic reticulum Expression of stress-related proteins (P-PERK, P-EIF2α, ATF4). Results Compared with the sham operation group, the neurological scores of the model group were significantly decreased (P <0.01). Compared with the model group, the scores of neurological function in the Qingkailing group, the UDCA group and the TUDCA group were significantly increased (P0.05, 0.01) . Compared with the sham-operation group, the model group had obvious ischemic focus (P <0.01). Compared with the model group, the volume of cerebral infarction in each group was significantly decreased (P <0.01). Compared with the sham group, the expression of P-PERK, P-EIF2α and ATF4 in the hippocampus and cortex of the model group were significantly increased (P <0.01). Compared with the model group, the levels of P -PERK, P-EIF2α, ATF4 expression, especially in Qingkailing, the decline of TUDCA most obvious. Conclusion The active ingredients of Bezoar can improve cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress. The effect of TUDCA is better than that of taurine and UDCA.