Aim of study:To investigate the alteration of contractile and relaxant responses of the isolated gastric smooth muscle in early diabetic rats,analyze the effects and mechanism of berberine on improving the neural function of gastric smooth muscle in diabetic rats.Material and methods:Male SD rats (200 g) were divided int0 5 groups:normal rats,diabetic rats,diabetic rats treated with high or low dose berberine by gavage and treated with berberine by intraperitoneal injection groups.Rats in diabetic group were fasted for 12h before administration streptozotocin (65mg·kg-1 in 1% sodium citrate buffer) by intraperitoneal injection.After two weeks of the streptozotocin administration,the rats in hig/low dose gavage group were given berberine (200/100mg·kg-1) by intragastric administration;rats in intraperitoneal injection group were injected berberine (20mg·kg-1),once a day for two weeks.Using the method of organ bath,contractile and relaxant responses were induced by electric field stimulation (EFS) and pharmacology agonist on gastric smooth muscle in rats,and the tool drugs were used to intervene in the neurotransmitter activity.Results:1.Changes of the symptoms and the functions of the gastric fundus smooth muscle in the early diabetic rats.Compared with normal rats,the drinking and urinating activities were increased in the diabetic rats,and the hair and tail colour were much darker;body weight was reduced (P<0.01),and the level of blood glucose was increased significantly There were no significant differences in the EFS-induced contractions on gastric body smooth muscle and the spontaneous contractions on gastric antrum in normal and diabetic rats (P>0.05).The reproducible and stable contractile responses were induced by EFS (20Hz),and could be completely blocked by lymol·L-1 atropine or O.1μmol·L-1 TTX on gastric fundus smooth muscle in normal rats;but in diabetic rats,the contractile responses were smaller,and the contractile amplitudes were apparently disordered,compared with that of in normal rats (P<0.05).The reproducible and frequency-dependent relaxant responses were induced by EFS (1-10Hz),and could be completely blocked by O.1μmol·L-1 TTX on gastric fundus smooth muscle and pylorus circular muscle in normal and diabetic rats.Compared with normal rats,FES-induced relaxations were significantly larger on gastric fundus smooth muscle in diabetic rats (P<0.01),but the contrary results were gotten on pylorus circular muscle (P<0.01).When the strips were pre-contracted by 0.3μmo1·L-1 carbachol,100μmol·L-1 L-NAME significantly inhibited EFS-induced relaxations on gastric fundus circular muscle,and no differences between the normal and diabetic rats (P<0.05),the percentage of inhibition on the relaxation was 94.8% and 93.7% at 1Hz,respectively.The EFS-induced relaxations were further inhibited when L-NAME combined with a-chymotrypsin or suramin (P<0.05).2.Effects of berberine on the functions of gastric fundus and pylorus circular muscle in diabetic rats and the related mechanisms Berberine corrected the disorder of contractile amplitudes and incresed the contractile responses induced by EFS on gastric fundus circular muscle in high dose gavage and intraperitoneal injection rats (P<0.05).The excessive enhancement of relaxant responses induced by EFS on gastric fundus smooth muscle were significantly improved in berberine high dose gavage group rats (P<0.01),but not in low dose gavage and intraperitoneal injection groups rats (P>0.05).Berberine improved the relaxant responses on pylorus circular muscle in high dose gavage and intraperitoneal injection groups rats,but not in low dose group Conclusions:1.Based on the changes of contractile and relaxant responses on gastric smooth muscle in STZ-induced diabetic 4 weeks rats,the distinct sensitivity in different parts of stomach indicates that the damages of gastric fundus and pylorus seem to occur first on gastric functional changes in early diabetic rats.On neurogenic contractile and relaxant responses induced by EFS,the cholinergic and nitrergic nerves were damaged,and purinergic component of the relaxant responses to EFS was enlarged on gastric fundus strips of diabetic rats.2.Berberine improves the functions of cholinergic and nitrergic nerve in early diabetic rats,which dominated the contraction and relaxantion of gastric smooth muscle.The regulated effects of berberine on cholinergic nerve were likely to depend in part on the regulation of nitrergic nerve.Different administration routes of berberine had different effects on gastric smooth muscle in diabetic rats;it may involve different metabolic pathways of berberine.