The Role Of PI3K/AKT/ ENOS Signaling Pathway In Slow Transit Constipation Of Rats

Objectives To evaluate the role of PI3K/AKT/e NOS signaling pathway in rats with slow transit constipation(STC).Methods 84 healthy SD rats were randomly divided into constipated group and control group,In the constipated group,the rats were administered with diphenoxylate(8mg/kg) daily to develop STC model,while the control rats were fed with normal saline.The number and the weight of fecal granule and the body weight of rats were recorded every 5 days.Transit functions of gastrointestinal movement were examined by an activated charcoal suspension pushing test one week after stopping the administration of diphenoxylate for 60 days and 90 days. Experimental determination of the biological function of colonic myoelectric activity in rats. ELISA assay were used to detect the content of NO and endothelial NO synthase(e NOS). Gastric antrum,small intestine,colon tissue were selected after rats’ dessection. P-Akt expression was observed by western blot;LY294002,the PI3 K blocker, NOS inhibitor L-NAME,were used to detecet the effects to the expression of P-Akt.Results Compared with control group, the daily number of fecal granule in the constipated group was fewer,the mean weight of each fecal granule was higher, the discharge time of the first granule of black faeces was longer(P<0.05). Colon of rats in the experimental group appeared slow bidirectional changes, the frequency of colon wave was significantly slowed down,increasing the amplitude waveform showed irregular, approximately sine wave-like curve. NO and NOS increased most in distal colon tissue.The expression of P-Akt in the distal colonic in the STC group was significantly reduced compared with control group(P<0.05), but not in stomach and small intestine.Compared with the model group,using the inhibitor LY294002 can reduce the expression of P-Akt(P<0.05),while the inhibitor L-NAME can increase the expression of P-Akt significantly(P<0.05).Conclusions The PI3K/AKT/eNOS signaling pathway is likely involved in the pathogenesis of rat STC,and this role is mainly by affecting the function of the distal colon tissue to complete.