Protective Effects Of Emodin On Intestinal Mucosal Barrier In Rat After I/R Injury And Mechanism

Intestinal ischemia-reperfusion participate pathogenesis of many kinds of clinical illnesses, which result in multiple organ failure, systemic inflammation response syndrome. Intestinal mucosal barrier which is constituted by mechanical, chemical, immune and microbial barriers, is the most important element in the intestinal I/R injury. Mechanical barrier is the foundation of intestinal barrier. Apoptosis is the most important style of intestinal death and the percentage is80%. In the process of development of intestinal I/R injury, apoptosis plays a very important role. The increase of intestinal mucosal apoptosis is relevant to intestinal I/R injury. A large amount of apoptosis lead to intestinal mucosal injury, increase of permeability of epithelium and translation of endotoxin and intestinal bacterium. The existing researches have demonstrated that endoplasmic reticulum stress is relevant to apoptosis and the endoplasmic reticulum stress path is one of the apoptotic paths. The endoplasmic reticulum stress path may participate in the intestinal mucosal I/R injury, is the important mechanism of intestinal I/R injury.Emodin is the active constituent of many traditional Chinese medicine, such as Polygonum and Rheum. The existing studies have demonstrated that emodin can obviously reduce the release of TNF-α、NO, cut down the activation and accumulation of neutrophil and reduce excess production of oxygen radicals to restrain excess inflammatory response and reduce intestinal mucosal I/R injury. We anticipate that emodin can restrain endoplasmic reticulum stress to reduce the intestinal mucosal apoptosis and the destruction of tight junction which are produced by intestinal mucosal I/R injury and protect intestinal mucosal barriers when I/R injury occurs.This research use I/R injury model of rat to investigate the effects of emodin on intestinal mucosal apoptosis and the destruction of tight junction after intestinal I/R injury and to investigate the effects of emodin on intestinal mucosal endoplasmic reticulum stress protein after intestinal I/R injury. We discuss the mechanism of protection of emodin on intestinal mucosal barrier after intestinal I/R injury to provide theoretical foundation of prevention and clinical cure of intestinal I/R injury.Study1. Protective Effects of Emodin on Intestinal Mucosal Barrier in Rat after I/R InjuryObjective To investigate the effects of emodin on intestinal mucosal barrier in rat after intestinal ischemia reperfusionMethods Forty-eight male SD rats were randomly divided into four groups: sham control group (S), model group (IR), model+saline group (IRS), model+emodin group (IRE).40mg/(kg*d) emodin was administrated intragastrically in IRE group for7days, the same volume saline was administrated intragastrically in IRS group.2hours after last administration, we established intestinal ischemia reperfusion model. Pathological changes of intestinal tissues and damages of tight junction were observed respectively by light microscopy and transmission electron microscopy in each group. Degree of injury to intestinal mucosa was evaluated by Chiu’s assessment. Intestinal mucosal apoptotic index was measured by TUNEL staining. Semi-quantitative assessment of Claudin-1and Occludin was measured by Western Blot.Results Pathological intestinal damages and tight junction damages were much lighter in IRE group than in IR group and IRS group. Degree of injury to intestinal mucosa and intestinal mucosal apoptotic index were significantly lower in IRE group than in IR group and IRS group (all P＜O.05). Contents of Claudin-1and Occludin were significantly higher in IRE group than in IR group and IRS group (all P<0.05).Conclusion Emodin can alleviate intestinal pathological damages, reduce cell apoptosis, protect intercellular tight junction and intestinal mucosal barrier in intestinal ischemia reperfusion rats.Study2. Mechanism of Protective Effects of Emodin on Intestinal Mucosal Barrier in Rat after I/R InjuryObjective To investigate the effects of emodin on intestinal mucosal endoplasmic reticulum stress protein after intestinal I/R injury. To discuss the mechanism of protection of emodin on intestinal mucosal barrier after intestinal I/R injury.Methods Forty-eight male SD rats were randomly divided into four groups: sham control group (S), model group (IR), model+saline group (IRS), model+emodin group (IRE).40mg/(kg*d) emodin was administrated intragastrically in IRE group for7days, the same volume saline was administrated intragastrically in IRS group.2hours after last administration, we established intestinal ischemia reperfusion model. Semi-quantitative assessment of GRP78and Caspase-12was measured by Western Blot.Results Contents of GRP78and Caspase-12were significantly higher in IR group and IRS group than in S group (all P＜O.05). Contents of GRP78and Caspase-12were significantly lower in IRE group than in IR group and IRS group (all P＜0.05).Conclusion I/R Injury can increase the expression of endoplasmic reticulum stress protein. Emodin can alleviate the increase so that emodin can restrain endoplasmic reticulum stress to protect intestinal mucosal barriers when I/R injury occurs.