Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis.
OBJECTIVE
Available experimental evidence from both clinical and animal models shows that both Chinese medicines tetrandine (Tet) and Qing Yi Tong (QYT) have positive treatment effects on acute pancreatitis (AP). This investigation was conducted to explore the treatment mechanisms of Tet and QYT on AP at the molecular level and thereby explain their therapeutic affects. It included an investigation of the effects of these drugs on gene expression of both intercellular adhesion molecule 1 (ICAM-1) and superoxide dismutase (Mn-SOD and Cu, Zn-SOD) in a rat model with AP.


METHODS
AP in the test rats was induced by subjecting them to laparotomy followed by a retrograde injection of 4 % sodium taurocholate into the bilio-pancreatic duct. The test rats with AP were divided into three groups. One was treated with Tet, one with QYT, and one with normal saline solution. The sham-operated control group (SO) rats were only subjected to laparotomy. They were given no further treatment. For the Tet group, Tet was injected intraperitoneally, and for the QYT group, QYT was given with a nose-gastric catheter. These procedures were done at both 10 min and 5 h after AP induction. The levels of ICAM-1 mRNA expression and of SOD (Mn-SOD and Cu, Zn-SOD) mRNA expression in the pancreas and liver tissues were measured by RT-PCR at 1, 5, and 10 h after AP induction.


RESULTS
When compared with the SO group during the observation time, rats with AP showed a higher expression of ICAM and a lower expression of Mn-SOD in both pancreas and liver tissues, and a lower expression of Cu, Zn-SOD in the pancreas. Tet treatment attenuated changes in the expression of both ICAM-1, and SOD (Mn-SOD and Cu, Zn-SOD) to a significant degree. A similar effect on the expression of SOD (Mn-SOD and Cu, Zn-SOD) was also found in the QYT group, but no obvious suppressive effect on ICAM-1 expression was observed.


CONCLUSIONS
The results of this study suggest that one of the main mechanisms of Tet and QYT in treating AP is to enhance anti-oxidation of the body. The results also suggest that the anti-inflammatory effect of Tet is involved in the reduction of ICAM-1 expression. This explains why Tet and QYT are beneficial in treating AP.
Li
Yong-Yu
YY
Department of Pathophysiology, Medical College of Tongji University, Shanghai 200331, China. liyyu@163.net
Li
Xue-Li
XL
Yang
Cui-Xiang
CX
Zhong
Hong
H
Yao
Hong
H
Zhu
Ling
L
D000208:Acute Disease; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D000470:Alkaloids; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C009438:tetrandrine; D013482:Superoxide Dismutase