Mechanism of nourishing yin and moistening intestine therapy for slow transit constipation based on PI3K/Akt pathway
[Objective]To explore the effect and mechanism of nourishing yin and moistening intestine in the treatment of slow transit constipation(STC)mice based on PI3K/AKT pathway.[Methods]The STC mice model was established by intragastric administration of loperamide hydrochloride.The 50 male ICR mice were randomly divided into normal group,model group,Ziyin Runchang Recipe low-dose group(1.3 g/kg),Ziyin Runchang Recipe high-dose group(2.6 g/kg)and positive drug group(Mosapili,3 mg/kg),with 10 mice in each group.Mice in each group were administrated by intragastric administration according to the corresponding drug concentration;normal group and model group were given equal doses of physiological saline by gavage,once a day while modeling,and fecal water content,time of first black defecation and intestinal transmission rate of mice in each group were detected after 14 consecutive days.The content of 5-hydroxytryptamine(5-HT)in colon tissue of each group was detected by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SCF and c-kit in colon tissues of mice were detected by RT-PCR.The protein expression levels of c-kit,PI3K,p-PI3K,Akt and p-Akt in colon tissues of mice were detected by Western blot.[Results]Compared with normal group,the first black defecation time of mice in model group was significantly extended(P＜0.05),fecal water content and intestinal transmission rate were significantly decreased(P＜0.05),and colon 5-HT content,c-kit and SCF mRNA levels were significantly decreased(P＜0.05).The expression levels of c-kit,P-PI3K/PI3K and P-Akt/Akt in colon were significantly decreased(P＜0.05).Compared with the model group,fecal water content of Ziyin Runchang Recipe high-dose group was significantly increased(P＜0.05),while that of Ziyin Runchang Recipe low-dose group and positive drug group had an increasing trend.The time of first black defecation in Ziyin Runchang Recipe high-dose group and positive drug group was significantly shortened(P＜0.05),and the time of first defecation in Ziyin Runchang Recipe low-dose group had a trend of shortening.The intestinal transmission rate of Ziyin Runchang Recipe in all dose groups and positive drug groups was significantly increased(P＜0.05).In colon tissues,the mRNA levels of c-kit and SCF in Ziyin Runchang Recipe high-dose group were significantly increased(P＜0.05),and the positive drug group had an increasing trend.The content of 5-HT and the expression of c-kit,p-PI3K/PI3K and p-Akt/Akt protein in Ziyin Runchang Recipe high-dose group and positive drug group were significantly increased(P＜0.05).[Conclusion]Ziyin Runchang Recipe can significantly improve intestinal transmission rate in the treatment of constipation,and its mechanism is related to increasing the content of 5-HT and the up-regulation of PI3K/Akt expression level,and then increasing the number of interstitial cells of Cajal.
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