Function of reticuloendothelial system on CCl4 induced liver injury in mice

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, alpha, beta and gamma-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, alpha value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and alpha values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.     

双环醇对对乙酰氨基酚致小鼠肝线粒体损伤的保护作用

目的观察双环醇对对乙酰氨基酚(acetaminophen,AP)引起小鼠肝脏线粒体损伤的保护作用.方法用AP诱发小鼠肝及肝线粒体损伤,测定血清转氨酶和观察肝形态病理学改变,判定双环醇对AP诱发肝损伤的保护作用;测定肝线粒体中谷草转氨酶(AST)和谷胱甘肽(GSH)的含量、肝线粒体膜的肿胀和流动性以及观察超微结构的变化,评定双环醇对线粒体损伤的保护作用.结果双环醇50,150mg@kg-1灌胃能保护AP引起的小鼠肝损伤,使血清转氨酶(ALT和AST)水平显著降低,肝脏形态的病理损伤减轻,防止肝线粒体中AST和GSH的降低以及肝线粒体超微结构的损伤,使线粒体膜的流动性以及肝线粒体对外加Ca2+引发肿胀的敏感性恢复正常.体外加药也能直接防止Ca2+及TritonX-100引发的线粒体膜肿胀.结论双环醇对AP引起的小鼠肝线粒体损伤具有明显的保护作用.     

赤芍甘草冲剂对D-半乳糖诱导肝损伤的保护作用

目的:探讨赤芍甘草冲剂对D-半乳糖胺(D-GalN)致小鼠急性化学性肝损伤的保护作用及可能机制。方法:建立D-GalN诱导小鼠化学性肝损伤模型,分光光度法检测血清中丙氨酸氨基转移酶(ALT)、天冬门氨酸氨基转移酶(AST)水平和肝匀浆丙二醛(MDA)、一氧化氮(NO)含量。结果:赤芍甘草冲剂(200、400、800 mg.kg-1)灌胃给药均能降低血清中升高的转氨酶水平,使升高的肝脾指数降低;同时发现赤芍甘草冲剂可降低肝匀浆中升高的MDA和NO水平。结论:赤芍甘草冲剂对D-GalN致小鼠急性化学性肝损伤具有保护作用,其机制与其抗氧化活性等有关。     

丙酮酸乙酯对利福平致小鼠肝损伤的保护作用

目的 探讨丙酮酸乙酯（EP）对利福平致小鼠肝损伤的保护作用及其可能机制。方法 24只C57BL/6小鼠随机分成3组：正常对照组、模型组（利福平,200 mg·kg^-1·d^-1） 和EP组（利福平200 mg·kg^-1·d^-1+丙酮酸乙酯40 mg·kg^-1·d^-1）,每组8只。造模后第7天处死小鼠,检测小鼠血清谷丙转氨酶（ALT）、总胆红素（TBIL）、直接胆红素（DBIL）、碱性磷酸酶（ALP）,观察小鼠肝脏病理学变化,检测小鼠肝组织总胆汁酸（TBA）、丙二醛（MDA）的含量、超氧化物歧化酶（SOD）活性、高迁移率族蛋白B1 （HMGB1） 及乙酰化的HMGB1（AC-HMGB1）蛋白的表达情况。结果 与正常对照组相比,模型组小鼠血清TBIL、DBIL、ALP、ALT水平升高（P<0.05）;肝细胞空泡变性、脂肪变性明显,部分肝细胞可见嗜酸性变、核溶解或固缩;肝组织TBA、MDA的含量提高（P<0.05）,SOD减少（P<0.05）,HMGB1及AC-HMGB1表达增多（P<0.05）,HMGB1胞浆表达为主。与模型组相比,EP组小鼠血清TBIL、DBIL、ALP、ALT水平降低（P<0.05）;肝组织病理学变化改善;肝组织TBA、MDA的含量降低（P<0.05）, SOD增多（P<0.05）,HMGB1及AC-HMGB1的表达水平降低（P<0.05）,HMGB1以胞核表达为主。结论 丙酮酸乙酯能够减轻利福平所致的小鼠肝损伤,其机制可能与丙酮酸乙酯抗氧化,下调肝组织HMGB1及AC-HMGB1的表达和调节HMGB1的分布有关。     

脱氢卡维汀对四氯化碳致小鼠急性肝损伤的保护作用

目的:对3种粒径的黄芪,采用4种不同的方法提取黄芪多糖及黄芪总皂苷,优选最佳粒径和提取方法.方法:对超微粉、200目细粉、饮片3种粒径的黄芪,分别采用水醇双提法、纤维素酶法、氧化钙溶液法、超声波法进行提取,用超滤法与D21大孔吸附树脂法进行分离,分别比较黄芪多糖及黄芪总皂苷的得率.结果:黄芪超微粉用超声波法提取黄芪多糖得率最高,达到1.73%;采用黄芪饮片用超声波法提取黄芪总皂苷得率最高,达到1.82%.结论:超声波提取方法对提取黄芪多糖和黄芪总皂苷的得率较其它方法都有较大的提高.黄芪的粒径越小对黄芪多糖提取得率越高,但对黄芪总皂苷的提取,随粒径减小而得率减少.     

铁甲草急性毒性实验及D-氨基半乳糖性肝损伤小鼠的影响研究

目的 观察铁甲草急性毒性反应;观察铁甲草水煎液作用于肝损伤小鼠后,对ALT、AST水平的影响.方法 铁甲草给予最大剂量,观察药物急性毒性反应;将小鼠随机分为高、低剂量组、阳性对照组、模型对照组和正常对照组,除了正常对照组,各组腹腔注射D-GalN造肝损伤模型后,各组连续给药5天,每天1次,末次给药1h后,取血清测定ALT和AST水平.结果 小鼠最大耐受剂量为150 g/kg,相当于临床用药的500倍,在该剂量下,动物一般状态良好,未见明显毒性反应症状;铁甲草水煎液高剂量组与模型组比较,ALT、AST水平差异有统计学意义,虽然铁甲草低剂量组与模型组ALT、AST值在统计学上没有显著性差异,但有减低的趋势.结论 小鼠最大耐受剂量下,没有明显急性毒性作用;铁甲草水煎液能降低肝损伤小鼠ALT、AST水平,提示铁甲草水煎液对肝损伤具有一定的保护作用,高剂量组作用明显优于低剂量组,说明了保护作用与剂量有关,作用机制有待于进一步深入探讨和研究.     

激动素对小鼠急性四氯化碳肝损伤的保护作用

目的:探讨激动素对四氯化碳(CCl_4)所致小鼠急性肝损伤的保护作用。方法:建立小鼠四氯化碳急性肝损伤模型,透射电镜观察肝组织超微结构,生化法测定肝组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量与血清丙氨酸转氨酶(ALT)活性、天冬氨酸转氨酶(AST)活性、清蛋白(Alb)含量,观察激动素对肝损伤的保护作用。结果:激动素(20,40 mg·kg~(-1)·d~(-1))能明显抑制肝细胞肿大、空泡变性和染色质增多边集,减轻肝损伤引起的线粒体、粗面内质网肿胀,抑制肝组织中SOD和CAT活性的降低和MDA含量的升高,提高肝组织抗氧化能力;同时激动素能降低血清ALT和AST活性,提高血清AIb含量。结论:激动素能够抵抗CCl_4所致小鼠急性肝损伤,其作用的发挥与清除自由基、提高抗氧化酶活性、维持细胞膜完整性有关。     

Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice

Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl(4))-induced liver injury. The mice were treated intraperitoneally with CCl(4) (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl(4). The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl(4) increased the level of circulating tumor necrosis factor-alpha markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl(4) treatment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl(4) increased the level of tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl(4)-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.     

姜黄及姜黄素对微囊藻粗毒素致急性肝损伤的化学预防作用

目的研究中药姜黄及姜黄素对微囊藻粗毒素致急性肝损伤的化学预防作用及机制。方法52只昆明种♂小鼠随机分为4组:姜黄组,20g·kg-1体重姜黄煎剂灌胃;姜黄素组,300mg·kg-1体重姜黄素灌胃;藻毒素组和对照组生理盐水灌胃,连续灌胃7d。d8,除对照组外,各组腹腔注射微囊藻粗毒素38.11μg·kg-1(0.6LD50),3h后处死动物,取肝制备肝匀浆,检测肝ALT、AST、LDH、ALP、GST、SOD和MDA水平,比较各组变化情况。结果藻毒素组肝匀浆中ALT、LDH、GST分别为(198.65±14.11)U·L-1、(597.47±124.95)U·L-1和(85.23±27.28)kU·g-1Pro,明显高于正常对照组(P<0.05);姜黄组分别为(178.40±13.46)U·L-1、(422.18±105.53)U·L-1和(55.86±13.39)kU·g-1Pro,姜黄素组分别为(168.41±16.13)U·L-1、(220.60±117.36)U·L-1和(54.22±23.87)kU·g-1Pro明显低于藻毒素组(P<0.05);藻毒素组SOD活性(2.08±0.38)kU·L-1明显低于正常对照组(2.62±0.25)kU·L-1(P<0.01),MDA水平为(1.74±0.30)mmol·g-1Pro,明显高于正常对照组(1.10±0.22)mmol·g-1Pro;(P<0.01);姜黄、姜黄素组肝SOD活性分别为(2.47±0.18)kU·L-1和(2.44±0.21)kU·L-1,肝MDA水平分别为(1.30±0.33)mmol·g-1Pro和(1.19±0.21)mmol·g-1Pro,与藻毒素组比较,差别有统计学意义(P<0.01)。其他指标各组之间无统计学意义。结论中药姜黄、姜黄素可明显降低微囊藻粗毒素染毒小鼠肝ALT、LDH和GST升高水平,明显提高染毒小鼠肝SOD活性,降低肝MDA水平,对藻毒素引起的肝脏过氧化损伤具有明显的保护作用。提示中药姜黄和姜黄素可望用于藻毒素等环境肝毒物的化学预防。     

诺丽果汁对四氯化碳引起肝损伤小鼠的肝保护作用

目的:观察大溪地诺丽果汁(Tahitian Noni Juice,TNJ)对四氯化碳(CCl4)引起的肝损伤小鼠的肝保护作用.方法:将50只小鼠分成空白对照,模型,TNJ小、中和大剂量5组,空白对照组和模型组用生理盐水灌胃,TNJ小、中、大剂量组分别用TNJ 5 g、10 g、20 g/kg体重灌胃,1次/d,连续7 d,第7 d模型组和TNJ小、中、大剂量组用20?l4花生油溶液0.1 ml/10 g体重皮下注射,造成肝脏损伤模型,第8 d分别测定空白对照组、模型组和TNJ小、中、大剂量组小鼠血清中的ALT、AST,体重变化,肝脏系数,硫喷妥钠引起小鼠睡眠时间的改变和观察肝细胞镜下病理改变.结果:TNJ能对抗CCl4引起的小鼠血清中的ALT和AST的升高,减轻CCl4对肝细胞的损害,模型组与空白正常对照组和TNJ组比较,差异均有显著性意义(P＜0.05和P＜0.01).结论:TNJ对CCl,引起的肝损伤有保护作用.     

水飞蓟素对伴刀豆球蛋白A致免疫性肝损伤小鼠的保护作用

目的研究水飞蓟素对伴刀豆球蛋白A(concanavalin A,Con A)诱导的免疫性肝损伤小鼠的保护作用,探讨其可能的肝保护机制。方法将实验小鼠30只随机分为对照组、模型组、水飞蓟素组(200 mg·kg~(-1)),各10只。对照组和模型组小鼠按10 m L·kg~(-1)灌胃0.5%羧甲基纤维素钠(CMC-Na)水溶液,水飞蓟素组小鼠灌胃同等容量的水飞蓟素(200 mg·kg~(-1),0.5%CMC-Na混悬),每日1次,共10 d。实验末期,模型组和水飞蓟素组小鼠尾静脉注射Con A(15 mg·kg~(-1))建立小鼠免疫性肝损伤模型,检测小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)活性及肝组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原型谷胱甘肽(GSH)、丙二醛(MDA)含量;苏木精-伊红(HE)染色法观察肝组织病理学变化。ELISA法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)和白细胞介素-6(IL-6)含量。结果水飞蓟素明显降低Con A所致免疫性肝损伤小鼠血清ALT、AST和ALP水平(P<0.01),还可增加肝组织SOD、CAT、GSH的活性,降低肝组织MDA水平(P<0.05或P<0.01),明显改善肝脏病理组织状况;显著降低小鼠血清TNF-α、IL-4和IL-6含量(P<0.01)。结论水飞蓟素能明显减轻Con A诱导的小鼠免疫性肝损伤,该作用与其增加肝组织中抗氧化酶的活性、降低脂质过氧化水平、降低TNF-α、IL-4和IL-6等促炎因子水平有关。     

利福平和异烟肼致小鼠肝损伤模型的特征研究

目的建立抗结核药物性肝损伤模型,为评价防治该类疾病的新药研究提供理想工具。方法分别单次灌胃小鼠利福平(RIF)100 mg·kg~(-1)或300 mg·kg~(-1),或连续灌胃RIF 300 mg·kg~(-1)、异烟肼(INH)150 mg·kg~(-1)或RIF 300 mg·kg~(-1)+INH 300 mg·kg~(-1) 1～3周,测定其生化及病理学指标。结果单次灌胃RIF后,小鼠血清总胆红素(TBIL)水平逐渐升高。连续给予INH 150 mg·kg~(-1)、RIF 300 mg·kg~(-1)或INH 150 mg·kg~(-1)+RIF 300 mg·kg~(-1) 1～3周均可明显增加小鼠肝脏指数,RIF单独或与INH联用均可升高小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及TBIL水平,肝脏组织出现空泡样病变。RIF与INH合用2周、3周时,在肝指数及ALT水平方面表现出明显的拮抗作用,在3周时对TBIL水平也表现出明显的相互拮抗作用,病理结果类似。结论 RIF是造成小鼠肝损伤的主导因素,与INH联用,INH具有拮抗RIF肝脏毒性的趋势。     

地顶孢霉菌丝体对四氯化碳所致小鼠急性肝损伤的保护作用

目的 研究地顶孢霉菌丝体(AMM)对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用.方法 建立CCl4诱导的小鼠急性肝损伤模型;观察AMM对血清中ALT和AST活性的影响及AMM对肝组织SOD、MDA、GSH-PX表达水平和肝、脾、胸腺指数的影响;HE染色观察AMM对CCl4小鼠肝脏形态学影响.结果 AMM(1 00...     

Isatidis Folium alleviates acetaminophen‐induced liver injury in mice by enhancing the endogenous antioxidant system

Isatidis Folium (IF) has been clinically combined with acetaminophen (APAP), but the rationality of combinational therapy is still ambiguous. In the present study, the protective effect and related mechanism of IF on APAP‐induced hepatotoxicity were evaluated. Hepatic histopathology and blood biochemistry investigations clearly demonstrated that IF could restore APAP‐induced hepatotoxicity. Liver distribution study indicated that the hepatoprotective effect of IF on APAP is attributed to the reduction of N‐acetyl‐p‐benzoquinone imine (NAPQI) in liver, which is a known hepatotoxic metabolite of APAP. Further study suggested the reduction is not via decreasing the generation of NAPQI through inhibiting the enzyme activities of CYP 1A2, 2E1, and 3A4 but via accelerating the transformation of NAPQI to NAPQI‐GSH by promoting GSH and decreasing GSSG contents in liver. Furthermore, IF significantly enhanced the hepatic activities of GSH‐associated enzymes in APAP‐treated mice. In summary, IF could alleviate APAP‐induced hepatotoxicity by reducing the content of NAPQI via enhancing the level of GSH and the followed generation of NAPQI‐GSH which might be ascribed to the upregulation of GSH‐associated enzymes.     

热休克预处理对对乙酰氨基酚所致小鼠急性肝损伤的保护作用

目的探讨热休克预处理对对乙酰氨基酚(AAP)诱导的小鼠急性肝损伤的保护作用。方法40℃分别热休克(HS)处理小鼠10min(HS10组)、20min(HS20组)和30min(HS30组),室温恢复8h后,小鼠ip给予AAP 550mg·kg-1诱导急性肝损伤,分别于AAP后0,6,24,42和72h进行相关指标检测。赖氏法检测小鼠血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性,HE染色进行病理学分析,免疫组化法检测给予AAP后0 h,小鼠肝热休克蛋白70(HSP70),细胞色素P4501A2(CYP1A2)和增殖细胞核抗原(PCNA)的表达,Western印迹法检测给予AAP后0,6,24,42和72h时小鼠PCNA的表达。结果与AAP对照组相比,HS20组小鼠血清中AST和ALT酶活水平显著降低(P<0.05),而HS10组和HS30组小鼠无显著差异。与AAP对照组相比,HS20显著降低了AAP诱导的小鼠肝损伤程度(P<0.05),而HS10和HS30未显著降低肝损伤的程度。HS20显著诱导了小鼠肝HSP70(P<0.01),CYP1A2(P<0.01)和PCNA(P<0.05)的表达,而HS10和HS30显著诱导了小鼠肝HSP70和CYP1A2(P<0.05)的表达,但未明显诱导PCNA的表达。与HS10和HS30相比,HS20更加显著地诱导了HSP70和CYP1A2的表达(P<0.05)。HS20组小鼠在注射AAP后0,6,24,42和72h,小鼠肝PCNA的表达均显著高于AAP对照组(P<0.05)、HS10和HS30组(P<0.05)。结论 40℃热休克预处理20min可以有效降低AAP诱导的小鼠急性肝损伤程度,加速肝损伤后的修复。     

富硒板党对小鼠CCl4致肝损伤的保护作用探讨

目的探讨富硒板党对小鼠四氯化碳（CCl4）致肝损伤的保护作用。方法采用CCl4致小鼠急性肝损伤模型,测定血清谷丙转氨酶（ALT）、谷草转氨酶（AST）,肝组织丙二醛（MDA）、超氧化物歧化酶（SOD）活性变化。结果富硒板党能保护CCl4所致小鼠肝损伤,表现为血清ALT,AST含量降低（P〈0.05或P〈0.01）和肝脏MDA含量下降（P〈0.01）,SOD活性增强（P〈0.05或P〈0.01）。结论富硒板党对CCl4所致小鼠肝损伤具有保护作用。     

The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice

Antitubercular drugs have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. In this study, we aimed to investigate the protective effects of ursodeoxycholic acid (UDCA) on liver injury caused by co-administration with isoniazid and rifampicin, two famous antitubercular drugs. Liver injury was induced by co-treatment with isoniazid (75 mg/kg) and rifampicin (150 mg/kg) for one week. Mice were orally administered with UDCA (15, 50 and 150 mg/kg) 30 min before isoniazid and rifampicin. We show that serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly increased in mice treated with isoniazid plus rifampicin. An obvious fatty accumulation, accompanied by mild necrosis and inflammation, was observed in liver of mice treated with rifampicin plus isoniazid. In addition, isoniazid plus rifampicin resulted in hepatic apoptosis, as determined by terminal dUTP nick-end labeling (TUNEL) staining and caspase-3 activation. Additional experiment showed that isoniazid plus rifampicin significantly increased the level of hepatic malondialdehyde (MDA) and caused glutathione (GSH) depletion and 3-nitrotyrosine (3-NT) residues in liver. UDCA pretreatment significantly attenuated isoniazid plus rifampicin induced oxidative stress in liver. Importantly, UDCA pretreatment significantly alleviated isoniazid plus rifampicin induced hepatic apoptosis. Moreover, UDCA-mediated anti-apoptotic effect seemed to be associated with its regulation of Bcl-2 and Bax gene expression in liver. These findings suggest that UDCA might protect against isoniazid and rifampicin induced liver injury through its anti-oxidative and anti-apoptotic effects.     

复方护肝颗粒对D-半乳糖胺诱导小鼠化学性肝损伤的保护作用

目的探讨复方护肝颗粒对D-半乳糖胺（D-GalN）致小鼠急性化学性肝损伤的保护作用及可能机制。方法建立D-GalN诱导小鼠化学性肝损伤模型，分光光度法检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平和肝匀浆丙二醛（MDA）、一氧化氮（NO）含量。结果复方护肝颗粒（20、40和80mg／kg）灌胃给药均能降低血清中升高的转氨酶水平，使升高的肝脾指数降低；同时发现复方护肝颗粒可降低肝匀浆中升高的MDA和NO水平。结论复方护肝颗粒对D-GalN致小鼠急性化学性肝损伤具有保护作用，其机制与其抗氧化活性等有关。     

正柴胡饮对对乙酰氨基酚所致小鼠急性肝损伤的保护作用

目的研究正柴胡饮(ZCH)对对乙酰氨基酚(APAP)所致小鼠急性肝损伤的保护作用。方法将ICR小鼠随机分为ZCH单次治疗给药组(0 h ig给予APAP,6 h ig给予ZCH)、ZCH多次治疗给药组(第1天ig给予APAP,第2天~第4天ig给予ZCH)、ZCH多次预防给药组(前3天ig给予ZCH,第4天ig给予APAP)。单次治疗给药组、多次治疗给药组及多次预防给药组均同时设正常对照组和APAP模型组(0 h ig给予APAP),单次治疗给药组同时设ZCH单独给药组(0 h ig给予ZCH)。APAP的给药量为500 mg·kg-1,ZCH的给药量以柴胡生药计约为36 g·kg-1。每组均在末次给药24 h后采集血浆样本,测定血浆中谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性,HE染色观察肝组织病变。利用液相色谱质谱联用技术、SIMCA及SPSS16.0软件进行血浆代谢组学分析。结果与正常对照组相比,模型组血浆GPT和GOT酶活性均显著升高(P<0.01),单独给药组血浆GPT和GOT活性均无显著差异;与模型组相比,单次治疗给药组、多次治疗给药组及多次预防给药组的GPT和GOT活性显著降低(P<0.01),但分别与正常对照组相比仍有显著差异(P<0.01)。病理切片结果显示,正常对照组和单独给药组均未见明显肝损伤。与模型组相比,单次治疗给药组肝损伤面积、多次治疗给药组肝损伤面积和多次预防给药组肝损伤程度明显减轻。偏最小二乘辨别分析法(PLS-DA)散点图表明,单次治疗给药组、多次治疗给药组和多次预防给药组分别远离APAP模型组,而向正常对照组方向移行。代谢谱结果表明,ZCH可调节由APAP引起的内源性物质变化,使其趋于正常,这些内源性物质涉及脂代谢、氨基酸代谢、糖代谢及能量代谢。结论 ZCH对由APAP所致的药源性肝损伤具有保护作用,代谢组学可灵敏、准确地预测肝损伤的发生发展,为临床合理用药及阐明其作用机制提供依据。