Protective Effect Of Polydatin On Experimental Acute Gastric Mucosal Lesion And Its Mechanisms

Acute gastric mucosal lesion (AGML)occurred in many pathologic situations, and the main injury factors include gastric acid and pepsase, drug, stress, ethanol, and operation, etc. Much attention was paid to the role of ischemia-reperfusion(IR)in the mechanism of acute gastric mucosal lesion recently.Polydatin(PD) is one of the effective ingredients extracted from Poligonum Cuspidatum Sieb. Et Zucc. It can be used to protect myocardium, enhance microcirculation and inhibit the aggregation of platelets. It also can prevent indotoxin shock, lower lipid, decrease superoxidation of lipid, and control cough, asthma and pathogen. The protective effect of PD on acute gastric mucosal lesion has not been reported at present. In this article, gastric mucosal lesion model of rats and mice induced by ethanol, CRS , GIRI were used to study the protective effects and its mechanism of PD in order to provide experimental basis for the further research and exploitation of PD.The main contents are as follows:1. Effects of PD on AGML induced by ethanol in mice AGML model induced by ethanol(0.1ml/10g)was used to evaluate the effects of PD. PD(120, 60, 30mg/kg, ig)successive administration 5 days before AGML could decrease gastric mucosal lesion area effectively(P<0.01 or P<0.05) .2. Effects of PD on gastric fluid, free acid, total acid and pepsase in the model of pylorus deligation in rats PD(40, 80mg/kg, ig) could not reduce gastric fluid, decrease free acid and total acid, and pepsase activity in rats of pylorus deligation(P>0.05, compared with model) . .3. Effects of PD on AGML induced by CRS in ratsPD(20, 40, 80mg/kg, ig)successive administration 5d could decrease gastric mucosal lesion index in rats, reduce MDA content and increase SOD and PGE2 level in the plasma(P<0.01 or P<0.05 , compared with model) .4. Effects of PD on gastric mucosal lesion induced by GIRI in ratsCompared with model group, PD(20, 40, 80mg/kg, ig)successive administration 5d could decrease gastric mucosal lesion area in rats. PD could relieve inflammatory cell infiltrate in gastric tissue and ameliorate the histopathological changes of gatric mucosa . PD(20, 40, 80mg/kg, ig)could raise NO and NOS content , also raise SOD, GSH-Px activity, lower MDA and MPO content in the gatric mucosa, decrease TNF-α, IL-1βcontent in the plasma and gatric mucosa of AGML rats by radio-immunoassay and RT-PCR. PD(40, 80mg/kg, ig)could reduce the vascular permeability as measured by extravasation of Evans blue dye(P<0.01 or P<0.05).Conclusions: PD could possess protective effect on experimental AGML. The protective effect may be mediated by antioxidative effect,anti-ischemia-reperfusion, inhibiting neutrophil infiltration, and reducing gastric mucosal vascular permeability. Its moleculal mechanism may relate to anti-oxygen derived free radical , increasing the level of PGE2, NO, NOS and decreasing the expression of proinflammatory cytokines such as TNF-αand IL-1β.