中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
10期
1414-1418
,共5页
张冠军%康品方%宗巧凤%于影%王芳芳%高琴
張冠軍%康品方%宗巧鳳%于影%王芳芳%高琴
장관군%강품방%종교봉%우영%왕방방%고금
糖尿病%肝损伤%乙醇%ALDH2%JNK通路%大鼠
糖尿病%肝損傷%乙醇%ALDH2%JNK通路%大鼠
당뇨병%간손상%을순%ALDH2%JNK통로%대서
diabetes%liver injury%ethanol%ALDH2%JNK pathway%rat
目的:观察激动线粒体乙醛脱氢酶2(aldehyde dehy-drogenase 2,ALDH2)对糖尿病大鼠肝脏损伤的保护机制,并分析JNK在其中的作用。方法健康♂ SD大鼠30只,随机分成3组:正常对照组、糖尿病组、糖尿病+线粒体乙醛脱氢酶2激动剂乙醇组。造模8周后测定空腹血糖和糖化血红蛋白水平,检测血清谷丙转氨酶(AST)、谷草转氨酶(ALT)的变化,HE染色观察肝脏病理结构改变,测定肝脏组织ALDH2、JNK、p-JNK蛋白的表达。结果与正常对照组比较,糖尿病组大鼠空腹血糖、糖化血红蛋白水平明显升高,血清AST、ALT水平升高,病理切片显示,肝小叶结构异常,肝细胞边界不清,细胞索排列紊乱,细胞肿胀,大量炎症细胞浸润,肝脏组织ALDH2蛋白表达降低,p-JNK、JNK蛋白表达增加,p-JNK/JNK比值增加。乙醇干预组与糖尿病组相比,大鼠空腹血糖、糖化血红蛋白水平无明显降低,血清AST、ALT水平降低,病理改变减轻,肝脏ALDH2蛋白表达增加, p-JNK、JNK蛋白表达降低,p-JNK/JNK比值降低。结论增加ALDH2的表达,可能通过抑制JNK的表达,减轻糖尿病对肝脏的损伤。
目的:觀察激動線粒體乙醛脫氫酶2(aldehyde dehy-drogenase 2,ALDH2)對糖尿病大鼠肝髒損傷的保護機製,併分析JNK在其中的作用。方法健康♂ SD大鼠30隻,隨機分成3組:正常對照組、糖尿病組、糖尿病+線粒體乙醛脫氫酶2激動劑乙醇組。造模8週後測定空腹血糖和糖化血紅蛋白水平,檢測血清穀丙轉氨酶(AST)、穀草轉氨酶(ALT)的變化,HE染色觀察肝髒病理結構改變,測定肝髒組織ALDH2、JNK、p-JNK蛋白的錶達。結果與正常對照組比較,糖尿病組大鼠空腹血糖、糖化血紅蛋白水平明顯升高,血清AST、ALT水平升高,病理切片顯示,肝小葉結構異常,肝細胞邊界不清,細胞索排列紊亂,細胞腫脹,大量炎癥細胞浸潤,肝髒組織ALDH2蛋白錶達降低,p-JNK、JNK蛋白錶達增加,p-JNK/JNK比值增加。乙醇榦預組與糖尿病組相比,大鼠空腹血糖、糖化血紅蛋白水平無明顯降低,血清AST、ALT水平降低,病理改變減輕,肝髒ALDH2蛋白錶達增加, p-JNK、JNK蛋白錶達降低,p-JNK/JNK比值降低。結論增加ALDH2的錶達,可能通過抑製JNK的錶達,減輕糖尿病對肝髒的損傷。
목적:관찰격동선립체을철탈경매2(aldehyde dehy-drogenase 2,ALDH2)대당뇨병대서간장손상적보호궤제,병분석JNK재기중적작용。방법건강♂ SD대서30지,수궤분성3조:정상대조조、당뇨병조、당뇨병+선립체을철탈경매2격동제을순조。조모8주후측정공복혈당화당화혈홍단백수평,검측혈청곡병전안매(AST)、곡초전안매(ALT)적변화,HE염색관찰간장병리결구개변,측정간장조직ALDH2、JNK、p-JNK단백적표체。결과여정상대조조비교,당뇨병조대서공복혈당、당화혈홍단백수평명현승고,혈청AST、ALT수평승고,병리절편현시,간소협결구이상,간세포변계불청,세포색배렬문란,세포종창,대량염증세포침윤,간장조직ALDH2단백표체강저,p-JNK、JNK단백표체증가,p-JNK/JNK비치증가。을순간예조여당뇨병조상비,대서공복혈당、당화혈홍단백수평무명현강저,혈청AST、ALT수평강저,병리개변감경,간장ALDH2단백표체증가, p-JNK、JNK단백표체강저,p-JNK/JNK비치강저。결론증가ALDH2적표체,가능통과억제JNK적표체,감경당뇨병대간장적손상。
Aim To observe whether the activation of aldehyde dehydrogenase 2 ( ALDH2 ) can protect a-gainst diabetes induced liver injury in rat model, and analyze the role of JNK pathway in the liver protection induced by activation of ALDH2 . Methods All male SD rats were randomly divided into three groups: nor-mal control group ( Con ) , diabetes group ( DM ) and ethanol + diabetes group ( EtOH + DM ) . After 8 weeks, the fasting blood glucose ( FBG) level, glyco-sylated hemoglobin ( HbA1c) level, serum AST and ALT levels were measured. The changes of hepatic pa-thology were observed by hematoxylin and eosin ( HE) staining method. The protein expressions of ALDH2, JNK and p-JNK in liver tissue were measured. Result Compared with control group, in DM group, the lev-els of FBG and HbA1c, serum AST and ALT levels were increased significantly. The structure of liver mor-phology was destroyed, disarranged and unclear, the hepatocyte was swollen, and a large number of inflam-matory cells were infiltrated. ALDH2 protein expres-sion was decreased, while the expressions of JNK, p-JNK and the ratio of p-JNK/JNK were increased. Com-pared with DM group, in EtOH+DM group, the levels of FBG and HbA1c, serum AST and ALT levels were decreased. The expression of ALDH2 protein was in-creased, accompanying with the decrease of JNK, p-JNK protein expressions and the ratio of p-JNK/JNK. Conclusion Activation of ALDH2 can protect the liv-er against diabetes induced liver damage in rat model, which may be relevant with inhibiting the JNK path-way.