BACKGROUND: To date, major hepatectomy with obstructive jaundice is still a highly risky and difficult surgery because of the high rate of complications. An excessive inflammatory response may be the primary hindrance to postoperative recovery of liver function. AIMS: Recent research has demonstrated that ulinastatin blocks the release of inflammatory factors and prevents the cytokine cascade reaction. This study was conducted to investigate the effect of ulinastatin on major hepatectomy after obstructive jaundice and to explore the potential mechanisms of this effect. METHODS: Male Sprague-Dawley rats were divided into three groups: sham, control and treated groups. In the control and treated groups, obstructive jaundice was induced, and a 70 % major hepatectomy was performed with implementation of ulinastatin treatment in the treated group but not the control group. The rats were sacrificed after hepatectomy on day 1, day 3, day 5 and day 7. The survival time, liver function, inflammatory cytokine expression and the indices of proliferation activities were examined. Kupffer cells were isolated, and the mRNA and protein levels of CD14 and NF-κB P65 in the Kupffer cells were determined. RESULTS: Compared to the control group, the survival rates, postoperative liver function, and the indices of proliferation activities were better in the treated group; in the treated group serum TNF-α and IL-6 levels were lower whereas serum IL-10 levels were higher. The expression of CD14 and NF-κB P65 in Kupffer cells at both the mRNA and protein levels was significantly higher in the control group than in the treated group. CONCLUSIONS: Ulinastatin has a protective effect in major hepatectomy with obstructive jaundice by inhibiting Kupffer cell activation and modulating the hepatic cytokine response.
BACKGROUND: To date, major hepatectomy with obstructive jaundice is still a highly risky and difficult surgery because of the high rate of complications. An excessive inflammatory response may be the primary hindrance to postoperative recovery of liver function. AIMS: Recent research has demonstrated that ulinastatin blocks the release of inflammatory factors and prevents the cytokine cascade reaction. This study was conducted to investigate the effect of ulinastatin on major hepatectomy after obstructive jaundice and to explore the potential mechanisms of this effect. METHODS: Male Sprague-Dawley rats were divided into three groups: sham, control and treated groups. In the control and treated groups, obstructive jaundice was induced, and a 70 % major hepatectomy was performed with implementation of ulinastatin treatment in the treated group but not the control group. The rats were sacrificed after hepatectomy on day 1, day 3, day 5 and day 7. The survival time, liver function, inflammatory cytokine expression and the indices of proliferation activities were examined. Kupffer cells were isolated, and the mRNA and protein levels of CD14 and NF-κB P65 in the Kupffer cells were determined. RESULTS: Compared to the control group, the survival rates, postoperative liver function, and the indices of proliferation activities were better in the treated group; in the treated group serum TNF-α and IL-6 levels were lower whereas serum IL-10 levels were higher. The expression of CD14 and NF-κB P65 in Kupffer cells at both the mRNA and protein levels was significantly higher in the control group than in the treated group. CONCLUSIONS:Ulinastatin has a protective effect in major hepatectomy with obstructive jaundice by inhibiting Kupffer cell activation and modulating the hepatic cytokine response.
Authors: Yong-Han Paik; Robert F Schwabe; Ramón Bataller; Maria P Russo; Christian Jobin; David A Brenner Journal: Hepatology Date: 2003-05 Impact factor: 17.425