加味四逆散对身心应激模型大鼠胃肠组织GASR、VIPR2mRNA表达的影响

目的:建立慢性应激性胃溃疡大鼠模型,探讨加味四逆散对应激模型大鼠胃液pH、胃黏膜溃疡指数(UI)、胃粘膜病理形态及胃组织胃泌素受体(GASR)和空肠组织血管活性肠肽II型受体(VIPR2)mRNA表达的影响,阐明加味四逆散干预应激性胃粘膜损伤的机制。方法:将Wistar大鼠60只随机分为正常对照组、模型对照组、奥美拉唑组、加味四逆散高、中、低剂量组,每组10只,采用慢性心理性应激方法建立应激性胃溃疡大鼠模型,经加味四逆散等干预后,检测胃液pH并评估胃黏膜溃疡指数(UI),常规HE染色镜下观察胃粘膜形态学改变,RT-PCR法检测胃组织GASR、空肠组织VIPR2mR-NA表达的变化。结果:与模型组比较,加味四逆散方各剂量组、奥美拉唑组大鼠胃液pH不同程度升高,而胃粘膜溃疡指数明显减小,差异均具有显著性意义(P<0.05~0.01);与奥美拉唑组比较,加味四逆散中、高剂量组胃液pH无显著性差异(P>0.05),而胃粘膜溃疡指数明显减小,差异有显著性意义(P<0.05~0.01);胃粘膜HE染色结果显示模型组大鼠胃粘膜弥漫出血、溃疡糜烂,较正常组损伤明显,加味四逆散高、中、低剂量组大鼠胃粘膜损伤较模型组不同程度减轻。正常组及各治疗组胃组织GASRmR-NA表达均较模型组升高,空肠组织VIPR2mRNA表达则降低,差异有统计学意义(P<0.05~0.01),加味四逆散中、高剂量组胃组织GASRmRNA表达均较奥美拉唑组明显升高,差异有统计学意义(P<0.05~0.01),中药高剂量组空肠组织VIPR2mRNA表达较奥美拉唑组则明显降低,差异有统计学意义(P<0.01)。结论:加味四逆散可显著减轻应激性胃粘膜损伤程度,抑制应激所致胃酸分泌,并可改善胃组织GASR、空肠组织VIPR2mRNA表达。

Effects of Jia-Wei-Si-Ni-San on GASR mRNA, Jejunal tissue VIPR2 mRNA Expression of Chronic Psychological Stress Rats Model

This study was aimed to establish a rat model of chronic stress ulcer, in order to discuss the effect of pH value of gastric juice, gastric mucosa ulcer index (UI), gastric mucosa pathological morphology, expression mRNA of gastrin receptor of gastric tissue (GASR) and vasoactive intestinal peptide II receptor (VIPR2) of jejunal tissue for the explanation of mechanism of Jia-Wei-Si-Ni-San (JWSNS) on the stress-induced gastric mucosal injury. A total of 60 Wistar rats were randomly divided into the normal group, model group, Omeprazole group,JWSNS large dosage, medium dosage and small dosage group, with 10 rats in each group. Stress gastric ulcer rat model was made by chronic psychological stress method. After JWSNS intervention, the pH value of gastric juice was detected for the assessment of the mucosal ulcer index (UI), and microscopy was used in the observation of morphological changes of conventionally HE staining gastric tissue, detection of mRNA expression changes of gastric tissue GASR, jejunal tissue VIPR2 of rats with RT-PCR method. The results showed that compared with the model group, the pH value of gastric juice of JWSNS high dosage, medium dosage, low dosage group, and omeprazole group rats were increased in different degree, the gastric mucosal ulcer index reduced significantly (P< 0.05 ~ 0.01). Compared with the omeprazole group, there were no significant difference of pH value of gastric juice between JWSNS medium and high dosage group (P > 0.05), and the gastric mucosal ulcer index reduced significantly (P < 0.05 ~ 0.01). HE staining showed that the gastric mucosa tissue of rats in the model group appeared diffuse bleeding ulcer compared with the normal group which indicates obvious injury. The gastric mucosa injury of JWSNS high dosage, medium dosage and low dosage group rats were severe than the model group. The gastric tissue GASR mRNA expression of the normal group and the treatment group were increased. And the jejunal tissue VIPR2 mRNA expression is lower compared with the model group. There was significant difference between groups (P < 0.05 ~ 0.01). The GASR mRNA expression of JWSNS high dosage, medium dosage and low dosage group were higher than that of omeprazole group with significant differences (P < 0.05 ~ 0.01). The jejunal tissue VIPR2 mRNA expression of high dose group was lower than the omeprazole group with significant difference (P < 0.01). It was concluded that JWSNS can significantly reduce gastric mucosal injury induced by stress through the inhibition of gastric acid secretion, improvement of the stomach, jejunum tissue VIPR2, GASR mRNA expression.