基于HPA轴探讨通腑降浊方治疗便秘型肠易激综合征模型大鼠的作用机制

Mechanism of Tongfu Jiangzhuo Formula in the treatment of IBS-C model rats based on HPA axis

目的:基于下丘脑-垂体-肾上腺(HPA)轴探讨通腑降浊方治疗实验性便秘型肠易激综合征(IBS-C)的作用和机制。方法:42只健康雄性SD大鼠随机分为6组,即正常组,模型组,西药组(3.6mg/kg,西沙必利)及通腑降浊方高、中、低剂量组(18.5、9.25、4.625g/kg)组,采用冰水灌胃法建立IBS-C大鼠模型,连续灌胃给药14d。采用结直肠球囊扩张(CRD)最小容量阈值法测定大鼠内脏敏感性。采用放射免疫法测定大鼠血清中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)与皮质酮(CORT)的含量。结果:治疗前,与正常组比较,其他各组大鼠CRD最小容量阀值均显著降低(P<0.05),治疗后,与正常组比较,模型组大鼠CRD最小容量阈值显著降低(P<0.05),血清中CRH、ACTH、CORT含量显著增加(P<0.05);与模型组比较,各治疗组大鼠CRD最小容量阈值显著增加(P<0.05),血清中CRH、ACTH、CORT含量显著降低(P<0.05)。结论:通腑降浊方治疗IBS-C的作用机制可能与改善HPA轴功能紊乱,进而改善肠道高敏状态有关。

Objective： To explore the effect and mechanism of Tongfu Jiangzhuo Formula on experimental constipationpredominant irritable bowel syndrome（IBS-C） based on hypothalamus-pituitary-adrenal（HPA） axis. Methods： According to random number table, 49 healthy male SD rats were divided into 6 groups： normal group, model group, Western medicine group（3.6 mg/kg, cisapride）, high dose of Tongfu Jiangzhuo Formula group（18.5 g/kg）, middle dose of Tongfu Jiangzhuo Formula group（9.25 g/kg）, low dose of Tongfu Jiangzhuo Formula group（4.625 g/kg）, with 7 rats in each group. The rats model with IBS-C was established by gavage with ice water, and then the rats were administrated by corresponding drugs for 14 days. The visceral sensitivity of rats was evaluated by the minimum capacity threshold of colorectal distension. The levels of corticotropin releasing hormone（CRH）, adrenocorticotropic hormone（ACTH）, cortisol（CORT） in serum of rats were detected by the radioimmunoassay. Results： Compared with normal group, the rats in other groups showed significant decrease in the minimum capacity threshold of colorectal distension before the treatment（P〈0.05）. Compared with normal group, the rats in model group showed significant decrease in the minimum capacity threshold of colorectal distension（P〈0.05）, and obvious increase in the levels of CRH, ACTH, CORT in serum after the treatment（P〈0.05）. Compared with model group, the rats in each treatment group showed significant increase in the minimum capacity threshold of colorectal distension after the treatment（P〈0.05）, and obvious decrease in the levels of CRH, ACTH, CORT in serum（P〈0.05）. Conclusion： The mechanism of Tongfu Jiangzhuo Formula in the treatment of IBS-C may be related to ameliorating the dysfunction of HPA axis and improving the state of intestinal hypersensitivity.