中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2014年
12期
948-952
,共5页
胡迎宾%彭娜%雷德利%程方雄%陈以莲
鬍迎賓%彭娜%雷德利%程方雄%陳以蓮
호영빈%팽나%뢰덕리%정방웅%진이련
炎症%c-Jun氨基末端激酶%胰岛素抵抗%凋亡
炎癥%c-Jun氨基末耑激酶%胰島素牴抗%凋亡
염증%c-Jun안기말단격매%이도소저항%조망
Inflammation%c-Jun N-terminal kinase%Insulin resistance%Apoptosis
目的 观察JNK抑制剂XG-102对高脂饮食诱导大鼠非酒精性脂肪性肝炎的治疗作用,并探讨其机制. 方法 通过手术对48只雄性SD大鼠建立经皮肠系膜上静脉给药通路,10d后将SD大鼠随机均分为对照组,模型组和治疗组.通过高脂饮食建立大鼠非酒精性脂肪性肝炎模型,其中治疗组在高脂饮食喂养12周后,同时给予JNK抑制剂XG-102(1 mg/kg)经皮肠系膜上静脉注射治疗4周.16周末观察肝脏病理组织学变化,检测血清ALT、AST、总胆固醇(TC)、甘油三脂(TG)、空腹胰岛素、空腹血糖、游离脂肪酸(FFAs)和肿瘤坏死因子α(TNF α)水平,计算稳态模型的胰岛素抵抗指数(HOMA-IR),用Westem blot方法检测肝组织phospho-c-Jun和cleavedcaspase-3蛋白的表达水平.两组间比较用t检验,多组间比较采用方差分析,均数间的两两比较采用Student-Newman-Keuls检验,并进行方差齐性检验.计数资料组间比较采用x2检验.结果 对照组ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α分别为(41.3±4.8) U/L、(96.9±9.8)U/L、(1.11±0.19) mmol/L、(0.74±0.11) mmol/L、(353.1±36.4) μmol/L、3.20±0.39、(6.74±1.21) pg/ml,模型组分别为(118.3±11.6) U/L、(163.9±16.2)U/L、(3.45±0.49)mmol/L、(1.89±0.25) mmol/L、(613.2±64.1)μmol/L、6.97±0.72、(25.01±5.37) pg/ml,治疗组分别为(86.5±8.3) U/L、(130.6±13.4) U/L、(2.62±0.32) mmol/L、(1.14±0.19)mmol/L、(512.1±51.9)μmol/L、4.34±0.48、(19.96±4.19) pg/ml.与对照组比较,模型组血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均升高,P值均＜0.05,差异均有统计学意义;与模型组比较,治疗组血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均降低,P值均＜0.05,差异有统计学意义.对照组肝组织phospho-c-Jun和cleaved caspase-3蛋白的表达分别为0.161±0.014和0.165±0.013,模型组分别为0.406±0.035和0.548±0.051,治疗组分别为0.226±0.021和0.341±0.029.与对照组比较,模型组phospho-c-Jun和cleaved caspase-3蛋白的表达显著升高,P值均＜0.05,差异均有统计学意义;与模型组相比较,治疗组phospho-c-Jun和cleaved caspase-3蛋白的表达降低,P值均＜0.05,差异均有统计学意义.结论 JNK抑制剂XG-102能够改善脂质代谢,减轻胰岛素抵抗,降低肝损伤,抑制肝细胞凋亡,从而实现对高脂饮食诱导大鼠非酒精性脂肪性肝炎的保护作用.
目的 觀察JNK抑製劑XG-102對高脂飲食誘導大鼠非酒精性脂肪性肝炎的治療作用,併探討其機製. 方法 通過手術對48隻雄性SD大鼠建立經皮腸繫膜上靜脈給藥通路,10d後將SD大鼠隨機均分為對照組,模型組和治療組.通過高脂飲食建立大鼠非酒精性脂肪性肝炎模型,其中治療組在高脂飲食餵養12週後,同時給予JNK抑製劑XG-102(1 mg/kg)經皮腸繫膜上靜脈註射治療4週.16週末觀察肝髒病理組織學變化,檢測血清ALT、AST、總膽固醇(TC)、甘油三脂(TG)、空腹胰島素、空腹血糖、遊離脂肪痠(FFAs)和腫瘤壞死因子α(TNF α)水平,計算穩態模型的胰島素牴抗指數(HOMA-IR),用Westem blot方法檢測肝組織phospho-c-Jun和cleavedcaspase-3蛋白的錶達水平.兩組間比較用t檢驗,多組間比較採用方差分析,均數間的兩兩比較採用Student-Newman-Keuls檢驗,併進行方差齊性檢驗.計數資料組間比較採用x2檢驗.結果 對照組ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α分彆為(41.3±4.8) U/L、(96.9±9.8)U/L、(1.11±0.19) mmol/L、(0.74±0.11) mmol/L、(353.1±36.4) μmol/L、3.20±0.39、(6.74±1.21) pg/ml,模型組分彆為(118.3±11.6) U/L、(163.9±16.2)U/L、(3.45±0.49)mmol/L、(1.89±0.25) mmol/L、(613.2±64.1)μmol/L、6.97±0.72、(25.01±5.37) pg/ml,治療組分彆為(86.5±8.3) U/L、(130.6±13.4) U/L、(2.62±0.32) mmol/L、(1.14±0.19)mmol/L、(512.1±51.9)μmol/L、4.34±0.48、(19.96±4.19) pg/ml.與對照組比較,模型組血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均升高,P值均＜0.05,差異均有統計學意義;與模型組比較,治療組血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均降低,P值均＜0.05,差異有統計學意義.對照組肝組織phospho-c-Jun和cleaved caspase-3蛋白的錶達分彆為0.161±0.014和0.165±0.013,模型組分彆為0.406±0.035和0.548±0.051,治療組分彆為0.226±0.021和0.341±0.029.與對照組比較,模型組phospho-c-Jun和cleaved caspase-3蛋白的錶達顯著升高,P值均＜0.05,差異均有統計學意義;與模型組相比較,治療組phospho-c-Jun和cleaved caspase-3蛋白的錶達降低,P值均＜0.05,差異均有統計學意義.結論 JNK抑製劑XG-102能夠改善脂質代謝,減輕胰島素牴抗,降低肝損傷,抑製肝細胞凋亡,從而實現對高脂飲食誘導大鼠非酒精性脂肪性肝炎的保護作用.
목적 관찰JNK억제제XG-102대고지음식유도대서비주정성지방성간염적치료작용,병탐토기궤제. 방법 통과수술대48지웅성SD대서건립경피장계막상정맥급약통로,10d후장SD대서수궤균분위대조조,모형조화치료조.통과고지음식건립대서비주정성지방성간염모형,기중치료조재고지음식위양12주후,동시급여JNK억제제XG-102(1 mg/kg)경피장계막상정맥주사치료4주.16주말관찰간장병리조직학변화,검측혈청ALT、AST、총담고순(TC)、감유삼지(TG)、공복이도소、공복혈당、유리지방산(FFAs)화종류배사인자α(TNF α)수평,계산은태모형적이도소저항지수(HOMA-IR),용Westem blot방법검측간조직phospho-c-Jun화cleavedcaspase-3단백적표체수평.량조간비교용t검험,다조간비교채용방차분석,균수간적량량비교채용Student-Newman-Keuls검험,병진행방차제성검험.계수자료조간비교채용x2검험.결과 대조조ALT、AST、TC、TG、FFAs、HOMA-IR화TNF-α분별위(41.3±4.8) U/L、(96.9±9.8)U/L、(1.11±0.19) mmol/L、(0.74±0.11) mmol/L、(353.1±36.4) μmol/L、3.20±0.39、(6.74±1.21) pg/ml,모형조분별위(118.3±11.6) U/L、(163.9±16.2)U/L、(3.45±0.49)mmol/L、(1.89±0.25) mmol/L、(613.2±64.1)μmol/L、6.97±0.72、(25.01±5.37) pg/ml,치료조분별위(86.5±8.3) U/L、(130.6±13.4) U/L、(2.62±0.32) mmol/L、(1.14±0.19)mmol/L、(512.1±51.9)μmol/L、4.34±0.48、(19.96±4.19) pg/ml.여대조조비교,모형조혈청ALT、AST、TC、TG、FFAs、HOMA-IR화TNF-α수평균승고,P치균＜0.05,차이균유통계학의의;여모형조비교,치료조혈청ALT、AST、TC、TG、FFAs、HOMA-IR화TNF-α수평균강저,P치균＜0.05,차이유통계학의의.대조조간조직phospho-c-Jun화cleaved caspase-3단백적표체분별위0.161±0.014화0.165±0.013,모형조분별위0.406±0.035화0.548±0.051,치료조분별위0.226±0.021화0.341±0.029.여대조조비교,모형조phospho-c-Jun화cleaved caspase-3단백적표체현저승고,P치균＜0.05,차이균유통계학의의;여모형조상비교,치료조phospho-c-Jun화cleaved caspase-3단백적표체강저,P치균＜0.05,차이균유통계학의의.결론 JNK억제제XG-102능구개선지질대사,감경이도소저항,강저간손상,억제간세포조망,종이실현대고지음식유도대서비주정성지방성간염적보호작용.
Objective To observe the impact of the JNK inhibitor XG-102 in a diet-induced rat model of non-alcoholic steatohepatitis.Methods Forty-eight Sprague-Dawley male rats were subjected to a percutaneous superior mesenteric vein retention catheter operation and fed with a standard diet for 10days,after which the rats were randomly divided into the following three groups:normal control (NC) group;high-fat (HF) model group; XG-102 treatment group.The HF group was fed an HF diet and treated with 0.9％ sodium chloride for 16 weeks.The XG-102 group was fed an HF diet for 16 weeks and simultaneously treated with XG-102 (1 mg/kg) once per day for 4 weeks.The levels of serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglyceride (TG),homeostasis model of assessmentinsulin resistance (HOMA-IR) and tumor necrosis factor-alpha (TNFα) were measured.Liver histological changes were observed.The protein expressions of phospho-c-Jun and cleaved caspase-3 were detected by western blotting.Results Compared with the NC group,the HF group showed significantly higher levels of serum ALT,AST,TC,TG,HOMA-IR and TNFα (P ＜ 0.05).Compared with the HF group,the XG-102 group showed significantly lower levels of serum ALT,AST,TC,TG,HOMA-IR and TNFα (P ＜ 0.05).The HF group also showed significantly higher protein expression of phospho-c-Jun and cleaved caspase-3 than the NC group (P ＜ 0.05) and the XG-102 group (P ＜ 0.05).Conclusion The JNK inhibitor XG-102 may ameliorate lipid metabolism,reduce insulin resistance,decrease liver injury and inhibit hepatocytes apoptosis.
