柴胡疏肝散对功能性消化不良大鼠胃窦组织中GRP78和c-JNK表达的影响

目的:探讨柴胡疏肝散对功能性消化不良(FD)大鼠胃窦组织内质网应激相关分子葡萄糖调节蛋白(GRP78)、c-Jun氨基末端激酶(c-JNK)的影响。方法:将36只大鼠随机分成正常组、模型组、柴胡疏肝散低浓度组、中浓度组、高浓度组、多潘立酮组,除正常组正常饲养外,其余组均以夹尾刺激法制成FD模型,然后于造模同一天开始分别予以对应药物水溶液灌胃(柴胡疏肝散低、中、高剂量分别为0.16 g/mL, 0.32 g/mL和0.64 g/mL、多潘立酮0.30 mg/mL),持续用药4周后,麻醉取胃,测定胃排空率,ELISA检测胃窦组织c-JNK、GRP78蛋白含量,qRT-PCR技术检测GRP78、c-JNK的mRNA表达情况。结果:(1)相对于正常组而言,模型组胃排空率明显降低(P﹤0.05);与模型组对比,柴胡疏肝散低、中、高浓度组及多潘立酮组胃排空率高(P﹤0.05);(2)相比正常组而言,模型组大鼠胃窦组织内GRP78、c-JNK蛋白表达明显升高(P﹤0.05);与模型组相比,柴胡疏肝散低、中、高浓度组及多潘立酮组胃窦组织内GRP78、c-JNK蛋白表达降低(P﹤0.05);(3) qRT-PCR结果显示模型组胃窦组织内GRP78、c-JNK的mRNA表达量较正常组升高(P﹤0.05);与模型组相比,各用药组GRP78、c-JNK的mRNA表达量降低(P均﹤0.05)。结论:柴胡疏肝散治疗功能性消化不良的机制可能与其能调控内质网应激分子GRP78、c-JNK有关。

Influences of Chaihu Shugan powder on expressions of GRP78 and c-JNK in gastric antrum tissue of rats with functional dyspepsia

Objective:To approach the influences of Chaihu Shugan powder on endoplasmic reticulum stress related molecules glucose-regulated protein(GRP78)and c-Jun N-terminal kinase(c-JNK)in gastric antrum tissue of rats with functional dyspepsia(FD). Methods:36 rats were randomly divided into normal group,model group,groups of low-,medium-and high-concentration of Chaihu Shugan powder and domperidone group. Except normal group was normally fed,the rest of groups were made into FD models by clip-tail stimulus method. Then from the beginning of same day of modelling,the FD models were given corresponding aqueous solution of drug respectively by gavage(The low,medium and high doses of Chaihu Shugan powder were respectively 0.16 g/mL,0.32 g/mL and 0.64 g/mL,and domperidone doses was 0.30 mg/mL,). After 4 weeks of continuous medication,the stomach was taken out by anesthesia,the gastric emptying rate was determined,the content of c-JNK and GRP78 protein in gastric antrum tissue was detected by ELISA,mRNA expressions of GRP78 and c-JNK were detected by qRT-PCR technology. Results:1. Relative to the normal group,the gastric emptying rate of model group was significantly reduced(P<0.05);compared with the model group,the gastric emptying rates of groups of low-,medium-and high-concentration of Chaihu Shugan powder and domperidone group were high(P<0.05).2. Relative to the normal group,the expressions of c-JNK and GRP78 protein in gastric antrum tissue of rats in model groupwere significantly elevated(P<0.05);compared with the model group,the expressions of c-JNK and GRP78 protein in gastric antrum tissue of rats in groups of low-,medium-and high-concentration of Chaihu Shugan powder and domperidone group were reduced(P<0.05).3. qRT-PCR results showed that mRNA expressions level of GRP78 and c-JNK in gastric antrum tissue of rats in model group were higher than the normal group(P<0.05);compared with the model group,mRNA expression levels of GRP78 and c-JNK in each drug group were reduced(P<0.05). Conclusion:The mechanism of Chaihu Shugan powder treating functional dyspepsia may be related to its regulating endoplasmic reticulum stress molecular GRP78 and c-JNK.