An emerging candidate for protecting patients from liver injury after abdomen surgery

Many patients worldwide are going to receive major abdomen surgery or intestine transplantation every year and expect to be afflicted with liver injury afterwards.

The finding of a research group headed by Professor Han Jing-Yan in China and reported in January 7, 2008 of the World Journal of Gastroenterology (volume 14, issue 1) may prove good news for them.

The study by Han Jing-Yan et al discovered Ginsenosaide Rb1 (R1) is able to prevent hepatic microcirculatory disturbance and subsequent liver injury in mice induced by intestine ischemia and reperfusion (I/R). R1 is one of the major effective ingredients of Panax notoginseng (PN), a traditional Chinese herb medicine frequently included in various compound Chinese medicines for treatment of liver injury and numerous other diseases in China and other Asian countries.

In 2005, Dr. Han was working on the effect and underlying mechanism of cardiotonic pills (CP) in cooperation with Prof. Toshifumi Hibi and Dr Yoshinori Horie in the Department of Internal Medicine, School of Medicine, Keio University, Japan. They revealed the beneficial effect of CP for improving gut I/R induced liver injury (Horie Y, Han JY, Mori S, Konishi M, Kajihara M, Kaneko T, Yamagishi Y, Kato S, Ishii H, Toshifumi Hibi. Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically. World J Gastroenterol 2005; 11(4): 511-515). However, CP is a compound Chinese medicine preparation that contains PN, and salvia miltiorrhiza and Borneol additionally. It was not clear at that time which one among the three ingredients is actually responsible for this action. The present report of Dr. Han¡¯s group shows R1, one of the major compounds of PN, protects against the gut I/R induced liver injury impressively.

In this study, the animal model is established by ligation of the superior mesenteric artery (SMA) in C57/BL mice for 15 min followed by 30 min reperfusion. The researchers apply several techniques to address the issue concerned. First, they take advantage of an inverted intravital microscope assisted by a 3CCD color camera and high speed video camera and laser confocal microscope. This enables a dynamic examination of the hepatic microcirculatory parameters under investigation in mouse subjected to gut I/R and observes the gut I/R imposed impairment in vascular diameter, red blood cell velocity, sinusoid perfusion and leukocyte rolling and adhesion is obviously alleviated or completely abolished by pretreatment with R1.

Secondly, immunofluorescent staining is used to examine the endothelial adhesion molecules E-selectin and ICAM-1. Finally, blood is collected for detecting the expression of adhesion molecules in leukocyte and the activity of hepatic enzymes, including LDH, ALT, and AST, and the concentration of pro-inflammatory mediators such as TNF-¦Á, IL-6 and monocyte chemotactic protein-1 (MCP-1). After careful evaluation, the researchers concluded R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury by inhibition of leukocyte rolling and adhesion, through depressing the expression of E-selectin in endothelium and CD18 in neutrophils. This result is of significance not only for better understanding the mechanism of the effect of PN and PN containing preparations, but also for R1 to be used to prevent liver injury originated from gut I/R.