加味四逆散对身心应激模型大鼠血浆促肾上腺皮质激素、皮质醇及胃组织学的影响

Effects of JWSNS on plasma adrenocorticotropic hormone and cortisol,and gastric tissue of chronic psychological stress rat models

目的探讨加味四逆散对应激性胃溃疡模型大鼠行为学及胃黏膜组织病理形态等的影响,阐明加味四逆散干预应激致胃肠功能障碍的机制。方法将Wistar大鼠60只随机分为正常组,模型组,奥美拉唑组,加味四逆散高、中、低剂量组,每组10只,正常组大鼠正常喂养不参与造模;模型组,奥美拉唑组及加味四逆散高、中、低剂量组大鼠均选取10种不可预知刺激因素施以刺激制备慢性心理应激性胃溃疡大鼠模型,造模共4周。造模第3周开始给药,加味四逆散低、中、高剂量组分别给予浓度为0.25、0.5、1.0 g/mL的加味四逆散,奥美拉唑组给予浓度为0.3 mg/mL的奥美拉唑,每天将配置好的中药煎剂和奥美拉唑混悬溶液各2 mL灌胃大鼠,正常组及模型组给予生理盐水2 mL灌胃大鼠,以上给药均为1次/d,共2周。第4周造模结束后观察其行为学变化,然后处理大鼠检测大鼠胃液pH值并评估胃黏膜溃疡指数,常规HE染色镜下观察胃组织形态学改变,放免法测定血浆促肾上腺皮质激素(ACTH)和血清皮质醇(CORT)的变化。结果与模型组比较,正常组和加味四逆散各剂量组大鼠垂直及跨格运动次数显著增加,差异有统计学意义(P<0.05,P<0.01);与模型组比较,加味四逆散各剂量组、奥美拉唑组大鼠胃液pH值不同程度升高,而胃黏膜溃疡指数明显下降,血中ACTH和CORT含量不同程度降低,差异均有统计学意义(P<0.05,P<0.01);与加味四逆散小剂量组比较,加味四逆散中、大剂量组胃液pH值不同程度升高,胃黏膜溃疡指数均显著下降,血中ACTH和CORT含量进一步降低(P<0.05,P<0.01);胃黏膜组织HE染色结果显示,模型组大鼠胃黏膜弥漫出血、溃疡糜烂,较正常组损伤明显,加味四逆散高、中、低剂量组大鼠胃黏膜损伤较模型组不同程度减轻。结论加味四逆散可增强身心应激模型大鼠抗应激适应能力,明显改善其活跃程度,显著减轻应激性胃黏膜损伤程度,抑制应激所致胃酸分泌,并可调节下丘脑-垂体-肾上腺轴的状态。

Objective To study the effects of JWSNS exert on behavior and gastric mucosa of stress rat model of chronic stress ulcer, and to elucidate the mechanism of stress - induced gastrointestinal dysfunction. Methods SixtyWistar rats were randomly divided into 6 groups： normal group, model group, omeprazole group, and large, median, small dose JWSNS groups. The subjects were stimulated with 10 kinds of unpredictable stimuli for 4 weeks for constructionof chronic psychological stress gastric ulcer model except for those in normal group. Since the 3rd week 0. 25,0. 5, and 1 g/mL JWSNS and 0. 3 mg/mL omeprazole were given to the subjects in large, median, small dose JWSNS groups, andomeprazole group, respectively, by 2 mL daily; whereas 2 mL saline was given instead in normal group and model group. Behavior observation and gastric mucosal ulcer index, plasma ACTH and CORT, and conventionally HE staining were carried out for analysis. Results Compared with model group, vertical and cross grid movement counts of rats from normal group and JWSNS groups were significantly increased （ P 〈 0. 05, P 〈 0. 01 ）. Compared with model group, significant al-leviation of gastric pH value and mucosal ulcer index were revealed in JWSNS groups and omeprazole group, with significant reduction in ACTH and CORT （ P 〈 0. 05, P 〈 0. 01 ）. So was between small JWSNS group and high or medianJWSNS group （P 〈 0. 05, P 〈 0. 01 ）. Diffuse bleeding ulcer was observed in model group, whereas it was alleviated in JWSNS groups. Conclusion JWSNS can enhance anti - stress adaptive capacity in stressed rat model, improve mood,reduce stressinduced gastric mucosal injury, inhibit gastric acid secretion, and regulate the state of HPA axis.