【摘要】 目的研究人工远端肢体缺血再灌注预处理(R-IPC)和缺血再灌注后处理(R-IPOST)对对乙酰氨基酚(APAP)诱导小鼠肝损伤的保护作用。方法按随机数字表法将实验小鼠分为5组:正常对照组(不做任何处理)、假手术组(缺血再灌注处理前后腹腔注射1ml生理盐水)、APAP组(腹腔注射1ml APAP溶液)、R-IPC+APAP组(缺血再灌注预处理后腹腔注射1ml APAP溶液)、R-IPOST+APAP组(腹腔注射1ml APAP溶液后实施缺血再灌注后处理)。观察各组肝脏病理形态变化;检测各组血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性、肿瘤坏死因子-a(TNF-a)水平、白细胞介素-6(IL-6)水平;检测各组肝组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽酶(GSH)的水平和比较各指标组间差异。结果光镜下R-IPC+APAP组和R-IPOST+APAP组肝小叶结构破坏程度及炎性细胞浸润程度较APAP组均明显减轻。R-IPC+APAP组血清ALT, AST, TNF-a, IL-6和肝匀浆MDA含量均明显低于APAP组[(3 742±519.7 U/L, 3 471±631.4U/L, 264.8±70.4pg/ml, 738.7±71.0 pg/ml, 8.9±1.2nmol/mg.prot)vs (5 564±621.7U/L, 4 647±813.9U/L, 351.7±52.3pg/ml, 929.7±140.6pg/ml, 13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=3.400～7.032,均P<0.05);R-IPC+APAP组肝匀浆SOD活性明显高于APAP组(11.0±1.9U/mg.prot vs 8.6±1.1U/mg.prot),差异有统计学意义(t=3.043, P<0.05);R-IPOST+APAP组血清ALT, AST, TNF-a, IL-6和肝匀浆MDA含量均明显低于APAP组[(3 410±588.6 U/L, 3 546±499.5U/L, 256.6±48.1pg/ml, 775.4±98.4pg/ml, 9.3±1.9nmol/mg.prot) vs(5 564±621.7U/L, 4 647±813.9U/L, 351.7±52.3pg/ml, 929.7±140.6pg/ml, 13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=2.196～4.981,均P<0.05);R-IPOST+APAP组肝匀浆GSH活性明显高于APAP组(10.3±1.2U/mg.prot vs 7.9±0.6U/mg.prot),差异有统计学意义(t=3.702, P<0.05)。结论 R-IPC和R-IPOST能降低APAP诱导的药物性肝损伤氧化应激和炎症反应程度,对肝功能具有保护作用。更多还原

【Abstract】 Objective To study the effect of artificial remote ischemia-reperfusion preconditioning(R-IPC) and remote ischemiareperfusion postconditioning(R-IPOST) on acetaminophen(APAP)-induced liver injury. Methods Five groups in this study: control group(mice remained untreated), sham operation group(mice subjected to remote ischemic conditioning manipulation and followed by an intraperitoneal injection of saline), APAP group(mice received intraperitoneal injection of 1 ml APAP), R-IPC+APAP group(mice subjected to R-IPC followed 5 min later by an injection of APAP), R-IPOST+APAP group(mice subjected to an injection of APAP followed 5 min later by R-IPOST). The pathological changes of liver were observed, Serum aminotransferase, alanine aminotransferase(ALT), Serum transaninase(AST)were detected. Malondialdehyde(MDA) content, superoxide dismutase(SOD) and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels, glutathione s-transferase(GSH), levels in liver tissue of each group were detected. Results The histopathological abnormalities were attenuated in R-IPC+APAP and R-IPOST+APAP group. The level of ALT, AST, TNF-a, IL-6 and MDA in R-IPC+APAP group were significantly lower than in APAP group[(3 742±519.7 U/L,3 471± 631.4 U/L,264.8± 70.4 pg/ml, 738.7±71.0 pg/ml,8.9± 1.2 nmol/mg.prot) vs(5 564± 621.7 U/L, 4 647±813.9 U/L, 351.7±52.3 pg/ml, 929.7±140.6 pg/ml, 13.1±1.7 nmol/mg.prot)], the difference were statistically significant(t = 3.400～7.032, all P<0.05). The SOD level was increased in R-IPC+APAP group than in APAP group(11.0±1.9 U/mg.prot vs 8.6± 1.1 U/mg.prot),the diffenence was statistically significant(t = 3.043, P<0.05). The level of ALT, AST, TNF-a, IL-6 and MDA in R-IPOST+APAP group were significantly lower than in APAP group[(3 410± 588.6 U/L, 3 546±499.5 U/L, 256.6±48.1 pg/ml, 775.4±98.4 pg/ml, 9.3±1.9 nmol/mg.prot) vs(5564± 621.7 U/L, 4647± 813.9 U/L, 351.7±52.3 pg/ml, 929.7± 140.6 pg/ml, 13.1±1.7 nmol/mg.prot)], the difference were statistically significant(t = 2.196～4.981,all P<0.05). The GSH level was higher in R-IPOST+APAP group than in APAP group(10.3±1.2 U/mg.prot vs 7.9±0.6 U/mg.prot),the difference were statistically significant(t = 3.702,P<0.05). Conclusion R-IPC and R-IPOST could reduce APAP-induced hepatic enzymatic activity and reduce inflammatory responses, which have protective effects on drug-induced liver injury.更多还原