A Series Of Studies On Protective Effects Of Short-term Starvation Preconditioning On Hepatic Ischemia Reperfusion Injury

Part I:A Research about Protective Effects of Short-term Starvation on Hepatic Ischemia/Reperfusion Injury in RatsOBJECTIVE:To observe the protective effects of short-term(1-3day)starvation pretreatment on hepatic ischemia/reperfusion injury in mice undergoing occlusion of hepatic blood flow.METHODS:48 male SD rats were randomized into eight groups(6/group),A:sham group with regular fasting,B:sham group with 1 day starvation,C:sham group with 2 day starvation,D:sham group with 3 day starvation,E:operated group with regular fasting,F:operated group with 1 day starvation,G:operated group with 2 day starvation,Hoperated group with 3 day starvation.The establishment of rat partial liver model of I/R injury,the samples were collected at 6h after the I/R,the serum ALT and AST levels were measured,the expression of TNF-a IL-6,IP-10,mRNA and MPO level in liver tissue were detected in liver by real-time PCR detection.RESULTS:The serum ALT and AST levels were significantly lower in 1d-ST,2d-ST,and 3d-ST mice compared to controls(P<0.05),especially in 2d-ST and 3d-ST mice(P<0.01).The expression of TNF-a mRNA in liver tissue were markly lower in 1d-ST,2d-ST and 3d-ST compared to controls(P<0.05),especially in 2d-ST and 3d-ST mice(P<0.01).The expression of IL-6,IP-1,and MPO levels were significantly lower in 2d-ST,and 3d-ST mice compared to controls(P<0.01),especially in 2d-ST.CONCLUSIONS:Hepatic I/R injury may occur in mice undergoing occlusion of hepatic blood flow.Short-term starvation may inhibit the expression of pro-inflammatory cytokines.Thereby alleviate hepatic I/R injury.Part ?:A Clinical Research about Protective Effects of Short-term Fasting on Hepatic Ischemia/Reperfusion InjuryOBJECTIVE:To observe the protective effects of short-term(24h)fasting pretreatment on hepatic ischemia/reperfusion injury patients undergoing excision of partial liver after occlusion of hepatic blood flow.METHODS:A prospective randomly controlled study was conducted.Eighty patients with liver tumor classified as Child-Pugh class A undergoing hepatectomy in the liver transplantation Center of the First Affiliated Hospital of Nanjing Medical University from April 2015 to May 2016 were enrolled.The patients were randomized into control group and experimental group(each patient received a 24huor-fasting,not fasting for water).Those patients then were divided into several subgroups by tumor size and time of clamping porta hepatis.Complete hepatic function were determined before and after operation(1,3 7d),Liver tissue was taken from resected specimen.Biochemical indexes were analyzed to evaluate liver injury.Cytokines(TNF-a,IL-6 and IL-10)were determined to assess inflammatory responses.In addition,oxidative stress was estimated by serum MDA and SOD levels.RESULTS:Compared with those indexes before operation,the postoperative levels afalanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TB)and direct bilirubin(DB)in control and fasting group were both significantly elevated,ALT level in fasting group after operation(1,3,7day)were significantly lower than those in control group(P<0.05).Although TB and DB in fasting group after operation(1,3 day)were lower than those in control group in different degrees(P<0.05),no statistical significance was found in total protein,albumin,and postoperative complications between the two groups(P>0.05).It was significant that postoperative levels of ALT(1,3day)in fasting group were lower than those in control group regardless of tumor size and time of clamping porta hepatis(P<0.05).Next,cytokines was analyzed,which interestingly showed TNF-a expression was significantly lower in hepatic tissues and serum in Fasting group compared with Ctrl group(P<0.05),but expression of IL-6 and IL-10 was not difference both groups.Furthermore,serum MDA was not significant difference at POD-1,but significant lower in Fasting group than Ctrl group at POD-3 and POD-7.Antioxidant molecule,SOD,was not obviously difference at POD-1 and POD-7,markedly higher at POD-3 in Fasting group compared with Ctrl group.CONCLUSIONS:Hepatic I/R injury may occur in patients undergoing resection of tumor with occlusion of hepatic blood flow.Short-term fasting may inhibit the release of serum pro-inflammatory cytokines and oxidative stress,thereby alleviate hepatic I/R injury.