Protective Function Of Notoginsenoside R1 In Intestinal Ischemia And Reperfusion Injury And The Relationship With NGF And ProNGF Signal Pathway

Intestinal transplantation is an effective treatment method to solve short bowel syndromle and a variety of end-stage of intestinal failure.Due to the special nature of their physiology,pathology and immunology,compared with other organs,the treatment effect is not obvious.Transplantation can produce intestinal ischemia and reperfusion injury phenomenon,and intestinal ischemia-reperfusion injury caused a series of intestinal lesions.Recent studies have found,Chinese herbology can relieve and treat intestinal ischemia-reperfusion injury.Objective:This experiment will investigate that the effect of the protection of Notoginsenoside R1 during intestinal ischemia and reperfusion in SD(Sprague Dawley)rats and the influence of NGF,TrkA,sortilin and p75NTR expression at the gene and protein levels.Methods:110 SD rats were randomly divided into four groups:sham-operation group rats),ischemia-reperfusion group,normal saline+ischemia-reperfusion group,and Notoginsenoside R1+ischemia-reperfusion treatment group.All mice were kept in ischemia for 30 minutes.According to the reperfusion time,they were divided into two sub-groups reperfused for 24h and 48h.We observed the height of intestinal mucosal and villus using HE staining by an optical microscope,and measured apoptotic intestinal cells selecting TUNEL method.Analyze the gene expression changes of NGF,TrkA,sortilin and p75NTR using Real-Time PCR method and the protein expression changes of NGF,TrkA,sortilin and p75NTR using western blot method.Results:(1)Compared with normal group(N group),saline + ischemia reperfusion group(group NS + I/R)and ischemia reperfusion group(I/R group),notoginseng saponins R1 treatment group(group NGR1)of small intestinal villus height are elevated.Mucosa and villous structures severely damaged.Compared with saline + ischemia reperfusion group(group NS + I/R)and ischemia reperfusion group(I/R group),notoginseng saponins R1 treatment group(group NGR1)of small intestinal villus height tends to the normal level.(2)48h reperfusion group of apoptosis cells more than 24h reperfusion group.After injection of panax notoginseng saponins R1 the number of apoptotic cells decrease.The number of apoptotic cells significantly reduced in reperfusion 48h and NGR1(10mg/kg)high dose group.Compared with normal group(N group),the mRNA and protein expression of NGF and TrkA reduced.After injecting NGR1 the expression of NGF and TrkA increase,and NGF and TrkA expression significantly improved in reperfusion 48h and NGR1(10mg/kg)high dose group.Compared with normal group(N group),sortilin and p75NTR mRNA and protein expression levels increase.After injecting NGR1 the expression of sortilin and p75NTR reduced.The expression of sortilin and p75NTR significantly down-regulated in reperfusion 48h and NGR1(10mg/kg)high dose groups.Conclusion:According to the changes of height and structure of intestinal mucosal and villus,it explained Notoginsenoside R1 protect intestinal ischemia-reperfusion injury in rats.After injection of different doses of NGR1,injected a dose of 10mg/kg,the extent of the damage of the small intestine significantly reduced,it describes that we can choose 10mg/kg dose to alleviate the extent of damage.By the expression of NGF,TrkA,sortilin and p75NTR,we conclude that Notoginsenoside R1 protects intestinal ischemia-reperfusion injury and improve intestinal function by regulating NGF and proNGF signaling pathways.