四磨汤对功能性消化不良肝胃不和证大鼠胃动力及RhoA/ROCK1信号通路的影响OA

Objective To explore the effects of Simo Decoction on gastric motility and the expression of molecules in the Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil-forming kinase1(ROCK1)signaling pathway in rats with functional dyspepsia(FD)of liver-stomach disharmony syndrome.Methods Thirty SPF male SD rats aged 2 to 3 months were randomly divided into blank group,model group,domperidone group,and high-,medium-and low-dose Simo Decoction groups using a random number table,with 5 rats in each group.Except for the blank group,rat models of FD with liver-stomach disharmony syndrome were established by tail-clamping stimulation in the other groups.Starting from the next day after modeling completion,rats in the domperidone group were intragastrically administrated domperidone solution at 0.32 mg/100 g;rats in the high-,medium-and low-dose Simo Decoction groups received Simo Decoction by gavage at doses of 5.6 g/kg,2.8 g/kg and 1.4 g/kg,respectively;rats in the blank and model groups were given equal volume of normal saline intragastrically,and all interventions lasted for 14 consecutive days.The general conditions and body weight of rats in each group were recorded during the experiment;gastric residual rate was measured;and histopathological changes in gastric tissues were detected using Hematoxylin-Eosin(HE)staining.Quantitative real-time PCRwere were used to detect the mRNA expression levels of molecules in the RhoA/ROCK1 signaling pathway in rat gastric tissues.Immunohistochemistry,and Western blot were used to detect the protein expression levels of molecules in the RhoA/ROCK1 signaling pathway in rat gastric tissues.Results Compared with the blank group,rats in the model group were irritable and agitated,frequently biting and fighting with each other,accompanied by dry,dark yellow and lusterless fur,remarkably reduced spontaneous activity with a tendency to curl up and lie still,as well as decreased appetite.Before modeling,there was no significant difference in body weight among all groups.After modeling,the body weight of rats in the model group,domperidone group,and three Simo Decoction groups decreased significantly relative to the blank group(P<0.01).After drug intervention,the body weight of the model group rats was still significantly lower than that of the blank group(P<0.01);compared with the model group,body weight markedly increased in the domperidone group and three Simo Decoction groups(P<0.01).Compared with the blank group,no obvious histopathological abnormalities were found in gastric tissues of all groups.The gastric residual rate of the model group was significantly higher than that of the blank group(P<0.01);compared with the model group,the gastric residual rates were significantly reduced in the domperidone group and three Simo Decoction groups(P<0.01).The expression levels of RhoA and ROCK1 in gastric tissues of the model group were obviously lower than those in the blank group(P<0.01).Compared with the model group,the mRNA expression of RhoA was up-regulated to varying degrees in the domperidone group and three Simo Decoction groups(P<0.01),and the protein expression level of ROCK1 in the high-and medium-dose Simo Decoction groups and the domperidone group significantly increased(P<0.05,P<0.01).Conclusion Simo Decoction can promote gastric emptying in FD model rats and exert a certain ameliorative effect on gastric motility in rats with FD of liver-stomach disharmony syndrome.Its therapeutic mechanism may be related to the up-regulated expression of RhoA and ROCK1.