Tang Guang-Hua, Yang Hua-Yu, Zhang Jin-Chun, Ren Jin-Jun, Sang Xin-Ting, Lu Xin, Zhong Shou-Xian, Mao Yi-Lei
Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
World J Gastroenterol. 2015 Nov 21;21(43):12370-80. doi: 10.3748/wjg.v21.i43.12370.
To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism.
We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively.
The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery.
High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.
探讨异甘草酸镁（MgIG）对大鼠肝大部切除动物模型的保护作用及其可能机制。
采用改良的埃蒙德法建立Sprague-Dawley大鼠标准90%肝切除模型，切除肝左叶、中叶、右上叶和右下叶。将90%肝切除的大鼠分为三组，分别腹腔注射3 mL生理盐水（对照组）、30 mg/kg（低剂量组）和60 mg/kg（高剂量组）MgIG。在不同时间点处死动物，从腔静脉取血。用自动生化分析仪进行生化检测，检测项目包括：血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶、总胆红素（TBil）、直接胆红素（DBil）、总蛋白、白蛋白、血糖（Glu）、超敏C反应蛋白、凝血酶原时间（PT）和凝血酶时间（TT）。每小时观察术后存活时间直至死亡。通过免疫组化分析肝细胞再生情况。采用酶联免疫吸附测定法（ELISA）分析血清炎性细胞因子（IL-1、IL-6、IL-10和诱导型一氧化氮合酶）。分别采用蛋白质印迹法和定量逆转录聚合酶链反应分析信号转导和转录激活因子3（STAT3）蛋白和mRNA水平。
与对照组和低剂量组相比，高剂量组的存活时间显著延长（22.0±4.7小时对8.9±2.0小时对10.3±3.3小时，P = 0.018）。术后6小时起，各组间ALT、Glu和PT水平存在显著差异。MgIG治疗组的ALT水平显著低于对照组。MgIG治疗组的Glu和PT水平均显著高于对照组。术后12小时，MgIG治疗组与对照组的ALT、AST、TBil、DBil和TT水平存在显著差异。未发现肝细胞再生有显著差异。与对照组相比，高剂量组血清炎性细胞因子IL-1和IL-10显著升高，IL-6降低。术后6小时、12小时和18小时，MgIG治疗组的STAT3蛋白和mRNA水平均显著低于对照组。
高剂量MgIG可延长大鼠肝大部切除术后的存活时间。这种肝保护作用是通过抑制STAT3途径从而抑制炎症反应来介导的。
