中文摘要：

目的观察c—jun氨基末端激酶（JNK）抑制剂SP600125对小鼠急性肝功能衰竭的保护作用。方法55只雄性C57／BL6小鼠采用随机数字表法分为实验组25只和对照组30只。实验组在腹腔注射D-半乳糖胺（D—GAIN）／脂多糖（1。PS）行肝功能衰竭造模前12h、lh皮下注射溶解于10％二甲基亚砜（DMSD）的JNK抑制剂SP600125，对照组在相同时间点皮下注射10％DMSO。两组分别干造模后0、2、4、6h各处死小鼠5只。免疫组织化学检测小鼠肝组织磷酸化JNK（p-JNK）、Caspase~3的表达情况。原位末端标记（TUNEL）染色观察肝组织中细胞凋亡情况。比较两组小鼠ALT水平、肝组织损伤程度及24h存活情况。组间比较采用t检验，生存率分析采用Kaplan—Meiey法。结果D—GalN／LPs造模后4h，实验组小鼠肝组织偶见p-JNK阳性细胞，对照组小鼠肝组织出现大量肝实质细胞表达rJNK。D—GalN／LPS造模后6h，实验组小鼠肝组织Caspase-3阳性细胞少见，对照组见满视野阳性细胞，实验组肝组织凋亡细胞计数为43．0±24．5，显著低于对照组的194．7±73．8（t=9．743，P-0．000）。实验组小鼠造模后6h，血清ALT水平为（214．o±54．7）U／L，显著低于对照组的（1234．4±478．4）U／I。（t=4．734，P=0．0015），肝组织损伤程度较轻，且24h5只小鼠存活4只，显著高于对照组的10只小鼠存活1只（x2=5．225，P=0．0223）。结论JNK抑制剂SP600125通过抑制JNK的激活，减少肝组织细胞凋亡，从而实现对胁GalN／I。PS诱导的小鼠急性肝功能衰竭的保护作用。

英文摘要：

Objective To investigate the protective effect of c jun N terminal kinase （JNK） inhibitor SP600125 against acute liver failure in mice. Methods Fifty five male C57/BL6 mice were divided into control group （n= 30） and SP600125 group （n： 25）. The animals were given an intraperitoneal injection of D-galactosamine （D-GaIN, 400 mg/kg body weight）/lipopolysaccharide （LPS, 30 p~g/kg body weight）. The control group and SP600125 group were given 10~ dimethyl sulfoxide （15 mL/kg body weight） or SP600125 （75 mg/kg body weight） subcutaneously 12 h and 1 h before D-GalN/LPS administration, respectively. D-GalN/LPS induced mouse JNK activation was detected by immunohistochemistry for phospho-JNK （p-JNK）. D-GalN/LPS induced mouse liver cell apoptosis was detected by immunohistochemistry for Caspase-3 and TdT-mediated-dUTP nick endlabeling （TUNEL）. Serum alanine transaminase （ALT） level was tested to assess liver injury. Survival rate of mice within 24 h after D-GalN/LPS administration was observed. The comparison between groups was done by t test and survival rate was analyzed by Kaplan-Meier method. Results JNK activity in liver tissues, as indicated by observation of p~JNK positive cells by immunohistochemistry, was diminished 4 h after D~GalN/LPS administration in SP600125 group. Reduced Caspase-3 activity was observed 6 h after D-GalN/LPS administration in SP600125 group （as indicated in immunohistochemistry by Caspase-3 positive cells）. Mice in SP600125 group showed significantly lower TUNEL-positive cell count than control group （43.04±24.5 vs 194.74±73.8 t：9. 743, P=0. 000）. Serum ALT level 6 h after D-GalN/LPS administration was （24.04±54.7） U/L in SP600125 group, which was significantly lower than that in control group [（1234.4±478.4） U/L t4. 734, P=0. 0015]. SP600125 also significantly improved the survival rate within 24 h after D-GalN/LPS administration （4/5 vs 1/10 X2 5. 225, P=0. 0223）. Conclusions JNK inhibitor SP600125 exerts protective effects