摘要目的:研究过氧化物酶体增殖物激活受体-γ(PPAR-γ)激动剂罗格列酮对重症急性胰腺炎(SAP)Sprague-Dawley(SD)大鼠肝细胞的作用和调控机制。方法:健康雄性清洁级SD大鼠72只，体质量255～315 g，鼠龄49～56 d，随机数字表法分为SAP模型组( n＝24，制备SAP模型)、罗格列酮组( n＝24，SAP模型制备后静脉注射罗格列酮)、假手术组( n＝24，仅注射生理盐水，不制备SAP模型)。模型制备后6、12、24 h取材，每批处理8只。HE染色观察肝组织改变，检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6和丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)浓度。Western印迹检测高迁移率族蛋白B1(HMGB1)、Janus激酶2(JAK2)、信号转导及转录活化因子3(STAT3)的表达。 结果:SAP模型组及罗格列酮组各时间点血清TNF-α、IL-1β、IL-6、AST、ALT、LDH水平均高于假手术组，差异均有统计学意义(均 P<0.05)。罗格列酮组6、12、24 h IL-1β分别为(226.5±52.1)ng/L、(458.2±82.3)ng/L、(556.4±83.4)ng/L，ALT为(158.3±39.2)U/L、(235.0±44.6)U/L、(298.4±56.6)U/L，低于SAP模型组(443.5±62.3)ng/L、(622.6±78.3)ng/L、(789.1±105.7)ng/L、(198.4±42.5)U/L、(253.8±47.0)U/L、(337.2±60.1)U/L，差异有统计学意义(均 P<0.05)。罗格列酮组各时间点AST、LDH也低于SAP模型组，差异有统计学意义(均 P<0.05)。HE染色罗格列酮组炎症、出血、坏死改变优于SAP模型组。罗格列酮组6、12、24 h STAT3的表达分别为(0.22±0.03)、(0.30±0.04)、(0.31±0.06)，低于SAP模型组(0.28±0.04)、(0.38±0.05)、(0.40±0.06)，差异有统计学意义(均 P<0.05)。罗格列酮组12、24 h JAK2、HMGB1的表达也低于SAP模型组，差异有统计学意义(均 P<0.05)。 结论:PPAR-γ激动剂罗格列酮能改善SAP大鼠肝细胞损伤和炎症程度，可能通过调节JAK2/STAT3通路发挥这种保护作用。

abstractsObjective:To study the effect of peroxisome proliferator activated receptor- γ (PPAR-γ) agonists rosiglitazone on the hepatocytes of Sprague Dawley (SD) rats with severe acute pancreatitis (SAP) and the regulatory mechanism.Methods:Seventy two healthy male SD rats, weighing 255-315 g, aged 49-56 days, were randomly divided into SAP model group ( n=24, SAP model preparation), rosiglitazone group ( n=24, rosiglitazone intravenous injection after SAP model preparation) and sham operation group ( n=24, normal saline injection only). After 6 h, 12h and 24 hours of injection, 8 rats were treated at each time point. HE staining was used to study the liver tissue structure and detect the levels of serum tumor necrosis factor-α(TNF-α), interleukin (IL) -1β, IL-6, AST, ALT and lactate dehydrogenase (LDH) in the rats. Western blot was used to detect the expression of high mobility group box-1 protein (HMGB1), Janus activated kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Results:The levels of serum TNF-α , IL-1β, IL-6, AST, ALT, LDH in SAP model group and rosiglitazone group were significantly higher than those in the sham operation group (all P<0.05). IL-1β at 6, 12h and 24 h in rosiglitazone group was (226.5±52.1)ng/L, (458.2±82.3)ng/L, (556.4±83.4) ng/L, ALT was (158. 3±39.2) U/L, (235.0±44.6)U/L, (298.4±56.6) U/L, which was lower than that in SAP model group (443. 5±62.3) ng/L, (622.6±78.3) ng/L, (789.1±105.7) ng/L and (198.4±42.5)U/L, (253.8±47.0)U/L, (337.2±60.1) U/L, the differences were statistically significant (all P<0.05). AST and LDH in rosiglitazone group were also lower than those in SAP model group at each time point, and the differences were statistically significant (all P<0.05). HE staining showed that there were less inflammation, hemorrhage and necrosis in rosiglitazone group than those in SAP model group. Expression of STAT3 in liver of rosiglitazone group at 6 h, 12 h and 24 h was (0.22±0.03), (0.30±0.04), (0.31±0.06), lower than SAP model group (0. 28±0.04), (0.38±0.05), (0.40±0.06), the differences were statistically significant (all P<0.05). Expression of JAK2 and HMGB1 in rosiglitazone group at 12 h and 24 h was also lower than that in SAP model group (all P<0.05). Conclusion:PPAR-γ agonists rosiglitazone can protect the SAP rats suffering from hepatocyte injury and inflammation, through JAK2/STAT3 pathway.