Abstract: Objective To investigate the effect of Ursolic acid on NOX2/ROS/NLRP3 inflammasome activation in carbon tetrachloride(CCl4)-induced liver fibrosis SD rat，and observe the improvement of collagen deposition in liver tissues. Methods All rats were randomly divided into 3 group: control group, CCl4 model group, UA treatment group. Liver fibrosis models SD rats were established by the CCl4-induced method and half of them was used as UA treatment group. Serum ALT was detected by ALT detection kit. The liver pathology and collagen deposition were observed by HE and Sirius-red staining. The mRNA expression of Nox2, Nlrp3, Caspase1, Il1β in liver tissues was detected by RT-qPCR. The protein expression of NOX2, NLRP3, caspase-1 and IL-1β in liver tissues was detected by Western blot and immunohistochemistry and the ROS generation in liver tissues were detected by DCFH-DA fluorescence probe. Results Compared with control group, in the CCl4 model group, the serum ALT was much higher (P＜0.05); the Ishak’s fibrosis score and collagen deposition was increased significantly(P＜0.05) and Nox2, Nlrp3, Caspase1, Il1β mRNA expression were increased. In addition, both the NOX2, NLRP3, caspase-1 p10 and IL-1β protein expression and ROS level (P＜0.05) of CCl4 model group were significant increased. Compared with CCl4 model group, the UA treatment group was found that the Ishak’s fibrosis score, collagen deposition and ALT decreased. Both mRNA expression of the Nox2, Nlrp3, Caspase1, Il1β and protein expression of NOX2, NLRP3, caspase-1 p10 and IL-1β as well as ROS were significant decreased, but the caspase-1 p45 protein level has no difference among all these groups (P＞0.05). Conclusion Ursolic acid attenuates the liver injury and reduces the collagen deposition, which may relate to its inhibitory effects on NOX2/ROS/NLRP3 inflammasome activation to reduce and release of IL-1β.

Key words: Ursolic acid, carbon tetrachloride, liver fibrosis, NADPH oxide 2, NLRP3 inflammasome