Effect of Gambogic Acid on Intestinal Injury in Septic Rats
Objective To investigate the effect of Gambogic Acid(GA)on intestinal injury in septic rats.Methods A total of 40 SPF SD rats were divided into Sham group,Sepsis group,Low-dose GA group and High-dose GA group according to the randomized numerical table method,10 rats in each group.The rat models of sepsis were established by cecal perforation ligation(CLP)in all three groups of rats except Sham group.Low-dose GA group and high-dose GA group were re-spectively given 50 and 100 mg·kg-1GA by gavage 24 h before modeling,and were anesthetized and executed 12 h after modeling,and peripheral blood and small intestinal tissues were collected.The expression levels of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β)and interleukin-6(IL-6)in serum were detected by enzyme-linked immunosorbent assay(ELISA);hematoxylin-eo-sin(HE)staining was used to observe the pathological changes in the small intestinal tissues and Chui's score were performed;Western blotting was used to detect the relative expression levels of apoptosis-related proteins(Caspase-3,Bax and Bcl2),tight junction proteins(ZO-1 and Occlu-din)and proteins related to RIP1/RIP3/MLKL signaling pathway.Results Compared with Sham group,the intestinal mucosa of the rats in Spesis group was significantly destroyed,and Chui's score was up-regulated(P＜0.05).Also,the levels of inflammatory factors(TNF-α,IL-1β and IL-6)in serum were significantly increased(P＜0.05);the relative expression levels of anti-apopto-sis protein Bax and tight junction protein zona(Claudin-1 and ZO-1)in small intestine tissue was significantly decreased(P＜0.05),while the relative expression levels of pro-apoptosis protein(Caspase-3 and Bcl2),and RIP1/RIP3/MLKL pathway-associated protein(MLKL,RIP1 and RIP3)were significantly increased(P＜0.05).Compared with Spesis group,the intestinal mucosal injury of rats in both Low-dose GA group and High-dose GA group showed different degrees of improvement,and Chui's score was down-regulated(P＜0.05).The levels of inflammatory factors(TNF-α,IL-1β and IL-6)in serum were significantly decreased(P＜0.05);the relative expression levels of anti-apoptosis protein Bax and tight junction protein zona(Claudin-1 and ZO-1)in small intestine tissue were significantly increased(P＜0.05),whereas the relative expression levels of pro-apoptosis protein(Caspase-3 and Bcl2)and RIP1/RIP3/MLKL pathway-associated protein(MLKL,RIP1 and RIP3)were significantly decreased(P＜0.05).Conclusion GA could alleviate sepsis-induced intestinal injury in rats,which may be closely related to RIP1/RIP3/MLKL signa-ling pathway.
万方数据
维普
