Protective mechanism of low dose of triptolide pretreatment against liver ischemia/reperfusion injury in mice / 中华器官移植杂志

ABSTRACT

Objective To investigate the protective effect of triptolide (TPT) pretreatment against liver ischemia/reperfusion (I/R) injury in mice and the possible mechanism. Methods Sixty male C57BL/6 mice were randomly divided into four groups (15/group) ( 1 ) TPT I/R group The mouse partial liver model of I/R injury was established by the method of Koba-yashi. The portal triad (hepatic artery, portal vein, and bile duct) was occluded with a microvascular clamp for 90 min and 24 h reperfusion; (2) Sham group with TPT Mice underwent surgical procedures including isolation of the portal triad without occlusion; (3) Saline I/R group Surgery was performed as the same in the TPT I/R group, (4) Sham group with saline Surgery was performed as the same in the TPT sham group, and the mice were pretreated with either saline or TPT (0. 1 mg · kg-1 day-1 ) by intraperitoneal injection for one week. The samples were collected at the 24th h after the I/R injury.The serum ALT and AST levels were determined, the histologic changes were observed by HE staining, the percentage of Th17 cells among mononuclear cells in liver tissue was analyzed by flow cytometry, the expression of IL-17 and ROR-γt mRNA was detected by real-time PCR, and the serum IL-6, IL-17 and TGF-β levels were measured by enzyme-linked immunosorbent assay (ELISA).Results Serum ALT and AST levels were significantly decreased and the histological damage was significantly alleviated in the TPT I/R group as compared with saline I/R group (P＜0. 05). The percentage of Th17 cells among mononuclear cells in TPT I/R group, TPT sham group, saline I/R group, TPT saline group was ( 1.77 ± 0. 53)％, (0. 41± 0. 18)％, (4. 26 ± 0. 82)％ and (0. 72 ± 0. 23) ％ in liver tissue, respectively. The expression levels of the IL-17 and ROR-γt mRNA in the liver tissue, and IL-6, IL-17 and TGF-β levels in the serum were significantly lower in TPT I/R group than in saline I/R group (P＜0. 05). Conclusion Pretreatment with low dose of TPT could effectively protect the liver from I/R injury in mice, which may be related to the inhibition of Th17 cells.