| Ischemia reperfusion injury is a histopathological process in anoxic organs recovering blood restoration and oxygen supply.It is necessary to block blood flow to the liver for a short-time or a long-time period in order to reduce blood loss,during the surgical operation of liver transplantation,severe liver trauma and lobe resection.With more understanding of basic medicine and in-depth studies on liver pathological physiological and metabolic processes,it has been found that liver ischemia reperfusion caused metabolism disorder in liver and whole body;and disturbed the hepatic synthe and secretion functions including blood coagulation,protein synthesis,and detoxification.The development of process needs to be terminated timely and effectively in order to prevent the occurrence of severe liver failure in terms of hepatic ischemia reperfusion injury(HIRI)which occurs after the recovery of hepatic blood inflow in reperfusion injury.HIRI often causes a variety of complications such as liver function damage,bile duct damage,and coagulation system disorder which remarkably affects the function recovery of liver and other organs after liver resection.Therefore,reducing hepatic ischemia reperfusion injury during liver operation is utmost important.Objective:This project aims at investigating the protective effect of ulinastatin treatment on hepatic portal blocking in patients undergoing resection ischemia reperfusion injury.Pringle method was used in liver cancer patients and the hepatic ischemia reperfusion injury indicators including the changes of liver enzymes,cytokines and histology,and ulinastatin treatment indicators change were measured,during the operation and the post-operation.Methods: A total of 75 patients with primary liver cancer who were underwent hepatic partial resection in the Tangshan Workers’ Hospital and the Tangshan Xiehe Hospital from January in 2015 to March in 2016,were randomly divided into 3 groups(25 patients each group).The experimental group A,sulinastatin(5000 U/kg in 50 ml saline)was pump into the internal jugular vein with 50 ml/h before cutting leather.The experimental group B,ulinastatin(10000 U/kg in 50 ml saline),was pump into the internal jugular vein with 50ml/h before cutting leather.The control group C,was carried out the normal operation process,without any drug treatment.Drug was dispensed by random configuration and the data was collected by surgeons and anesthesiologists.Data analyses were in a double-blinded manner.The blood samples(5 ml)were collected from the middle venous after induction of three groups patients in preoperative anesthesia,without application of ulinastatin(T1),after operation(T2),post-operation Day1(T3),post-operation Day3(T4),respectively.These blood samples were used to detect liver function(ALT,AST,ALB)index,serum cytokine interleukin-6(IL-6)and interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and plasma nitric oxide/endothelin-1(NO/ET-1)level.Independent sample test was used for the comparison between hemodynamic indexes and serum levels of inflammatory cytokines among groups at the same time point.The variance of repeated measurement was used for the comparison of serum inflammatory factor levels at the different times within groups.P<0.05 was considered significant difference statistically.Results: 1 General data’s statistical results,different groups of patients with no significant differences in terms of general information(P>0.05);2 At different time points,detect patients’ conditions of hemodynamic index MAP、HR、CVP,there is no significant degree of changes can be seen for different groups of patients at different time points for index data such as MAP,HR and CVP etc.(P>0.05);3 Ulinastatin’s effects on different groups of patients with liver enzymes,ALB’s content distinction is not clear and statistical difference does not exist(P>0.05).In terms of T1,there is no statistical differences of patients ALT and AST’s contents when comparing Experiment Group A and Experiment Group B.(P<0.05)However,when it comes to T2,T3 and T4,decreases can been observed regardless of Group A or Group B compared to Group C(P<0.05)and Group B’s average decrease is more apparent compared to Group A(P<0.05);4 Effect of ulinastatin on different patients’ IL-6 levels,no significant differences among the three groups during the operation(P>0.05).However,apparent differences can be seen at times between and post operation among the three groups(P<0.05).Each group’s serum IL-6 is the lowest value pre-operative and reaches peak level between operations,then starts a downward trend.Group A and B’s IL-6 level is lower than Group C with statistical differences(P<0.05),Group B’s IL-6 level is lower than Group A(P<0.05);5 Effect of ulinastatin on different patients’ TNF-α levels,no significant differences among the three groups during the operation(P>0.05).However,apparent differences can be seen at times between and post operation among the three groups(P<0.05).Each group’s serum TNF-α level is the lowest in the preoperative stage,reaches peak between operations,then shows a downward trend.Group A and B’s TNF-α level is lower than Group C with statistical differences(P<0.05).Group B is apparent lower than Group A(P<0.05);6 Effect of ulinastatin on different patients’ IL-10 levels,no significant differences among the three groups during the operation(P>0.05).However,apparent differences can be seen at times between and post operation among the three groups(P<0.05).Each group’s serum IL-10 level is the lowest in the preoperative stage,reaches peak between operations,then shows a downward trend.Group A and B’s IL-10 level is higher than Group C with statistical differences(P<0.05).Group B is apparent higher than Group A(P<0.05);7 Effect of ulinastatin on different patients’ NO levels,no significant differences among the three groups at T1(P>0.05).There were significant differences among the 3 groups(P<0.05)at the time of the T2,T3.Serum NO in each group decreased after operation,and then showed a rising trend.Group A,B at T2 and T3 higher than C group(P<0.05).Group B was significantly higher than that of group A(P<0.05)and at T4 groups were back to the level of T1(P>0.05);8 Effect of ulinastatin on different patients’ ET-1 levels,no significant differences among the three groups at T1(P>0.05).The serum ET-1 in each group was the lowest after the operation,and then decreased.Among them A,B two groups of ET-1 lower than the C group at T2,T3(P<0.05),The change of ET-1 in B group was significantly higher than that in A group(P<0.05),T4 was back to T1 level(P>0.05).Conclusions:1 By observing HCC patients’ partial hepatectomy among different points in time and their respective experiment levels of liver function index(AST、ALT、ALB)、Serum Cytokine Interleukin-6(IL-6)、Interleukin-10(IL-10)、Tumor Necrosis Factor-a(TNF-α)、 Plasma Nitric Oxide(NO)and Endothelin-1(ET-1),which can explain the partial hepatectomy hepatic ischemia-reperfusion injury caused by impaired liver function has significant inflammatory response.2 Found partial hepatectomy UTI can inhibit the generation of inflammatory cytokines,(IL-6、TNF-α)promote anti-inflammatory cytokine(IL-10)expression,Alleviated ischemia-reperfusion injury in the process of living liver cell damage,lowered transaminase,which played a role in liver protection.3 Ulinastain in partial hepatectomy operations inhibiting IL-6,TNF-α production and promote the expression of IL-10,can make NO concentration decreased and ET-1 elevated concentration much lower,which protect the liver function and plays a significant anti-inflammatory effects,the protective effect is stronger with high doses of ulinastatin. |
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