中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
Chinese Journal of Hepatology
2015年
9期
688-693
,共6页
朱月永%吴佳蓉%郑琦%董菁%江家骥
硃月永%吳佳蓉%鄭琦%董菁%江傢驥
주월영%오가용%정기%동정%강가기
过氧化物酶体增殖物激活受体%非诺贝特%细胞凋亡%非酒精性脂肪性肝病
過氧化物酶體增殖物激活受體%非諾貝特%細胞凋亡%非酒精性脂肪性肝病
과양화물매체증식물격활수체%비낙패특%세포조망%비주정성지방성간병
Peroxisome proliferator-activated receptor%Fenofibrate%Cell apoptosis%Nonalcoholic fatty liver disease
目的 通过高脂饲料喂养SD大鼠建立非酒精性脂肪性肝病(NAFLD)模型,观察过氧化物酶体增殖物激活受体(PPAR)激动剂非诺贝特对NAFLD大鼠肝脂肪变的影响并探讨可能的机制.方法 将66只雄性SD大鼠适应性喂养1周后,随机分为3组:对照组(C组,n=18)、模型组(M组,n=24)和非诺贝特组(F组,n=24).在实验的第4、6、8周时,分别处死1/3的各组大鼠,观察各组大鼠肝脏脂肪变性及炎症程度,观察肝细胞凋亡程度;检测肝组织中PPAR-αmRNA相对表达量及Bcl-2、Bax和Caspase-3 mRNA和蛋白的表达.多组间比较采用单因素方差分析(one-way ANOVA)法;等级资料采用Kruskal-Wallis H非参数检验进行分析;相关性分析采用Pearson相关分析和spearman秩相关分析两种方法.结果 与C组大鼠相比,随造模时间的延长,M组大鼠肝细胞脂肪变加重;炎症活动度计分升高(1.62±0.92对比0,P＜0.01);肝细胞凋亡指数升高(58.86±13.59对比39.55±3.99,P＜0.05),差异均有统计学意义.与C组大鼠比较,M组大鼠PPAR mRNA相对表达量降低(0.366±0.068对比0.570±0.061),Bcl-2 mRNA和蛋白的表达均减低(0.234±0.099对比0.437±0.053和0.0098±0.0002对比0.0155±0.0004),P值均＜0.01,差异均有统计学意义;Bax、Caspase-3 mRNA相对表达量(0.368±0.064对比0.230±0.052和0.363±0.058对比0.218±0.031)和蛋白表达(0.1311±0.0050对比0.0947±0.0139和0.1297±0.0065对比0.0794±0.0038)均明显增高,P值均＜0.01,差异均有统计学意义.F组大鼠肝细胞凋亡指数降低,肝组织PPAR mRNA和Bcl-2 mRNA和蛋白的相对表达量分别为0.510±0.109、0.425±0.042、0.0148±0.0004,与M组大鼠比较,P值均＜0.01,差异均有统计学意义;Bax、CaspaSe-3 mRNA和蛋白相对表达量为0.249±0.034、0.226±0.055、0.0966±0.0069和0.0911±0.0136,与M组大鼠比较,P值均＜ 0.01,差异均有统计学意义. 结论 非诺贝特可减轻NAFLD大鼠肝脂肪变性,其机制可能与抑制NAFLD大鼠肝细胞凋亡有关.
目的 通過高脂飼料餵養SD大鼠建立非酒精性脂肪性肝病(NAFLD)模型,觀察過氧化物酶體增殖物激活受體(PPAR)激動劑非諾貝特對NAFLD大鼠肝脂肪變的影響併探討可能的機製.方法 將66隻雄性SD大鼠適應性餵養1週後,隨機分為3組:對照組(C組,n=18)、模型組(M組,n=24)和非諾貝特組(F組,n=24).在實驗的第4、6、8週時,分彆處死1/3的各組大鼠,觀察各組大鼠肝髒脂肪變性及炎癥程度,觀察肝細胞凋亡程度;檢測肝組織中PPAR-αmRNA相對錶達量及Bcl-2、Bax和Caspase-3 mRNA和蛋白的錶達.多組間比較採用單因素方差分析(one-way ANOVA)法;等級資料採用Kruskal-Wallis H非參數檢驗進行分析;相關性分析採用Pearson相關分析和spearman秩相關分析兩種方法.結果 與C組大鼠相比,隨造模時間的延長,M組大鼠肝細胞脂肪變加重;炎癥活動度計分升高(1.62±0.92對比0,P＜0.01);肝細胞凋亡指數升高(58.86±13.59對比39.55±3.99,P＜0.05),差異均有統計學意義.與C組大鼠比較,M組大鼠PPAR mRNA相對錶達量降低(0.366±0.068對比0.570±0.061),Bcl-2 mRNA和蛋白的錶達均減低(0.234±0.099對比0.437±0.053和0.0098±0.0002對比0.0155±0.0004),P值均＜0.01,差異均有統計學意義;Bax、Caspase-3 mRNA相對錶達量(0.368±0.064對比0.230±0.052和0.363±0.058對比0.218±0.031)和蛋白錶達(0.1311±0.0050對比0.0947±0.0139和0.1297±0.0065對比0.0794±0.0038)均明顯增高,P值均＜0.01,差異均有統計學意義.F組大鼠肝細胞凋亡指數降低,肝組織PPAR mRNA和Bcl-2 mRNA和蛋白的相對錶達量分彆為0.510±0.109、0.425±0.042、0.0148±0.0004,與M組大鼠比較,P值均＜0.01,差異均有統計學意義;Bax、CaspaSe-3 mRNA和蛋白相對錶達量為0.249±0.034、0.226±0.055、0.0966±0.0069和0.0911±0.0136,與M組大鼠比較,P值均＜ 0.01,差異均有統計學意義. 結論 非諾貝特可減輕NAFLD大鼠肝脂肪變性,其機製可能與抑製NAFLD大鼠肝細胞凋亡有關.
목적 통과고지사료위양SD대서건립비주정성지방성간병(NAFLD)모형,관찰과양화물매체증식물격활수체(PPAR)격동제비낙패특대NAFLD대서간지방변적영향병탐토가능적궤제.방법 장66지웅성SD대서괄응성위양1주후,수궤분위3조:대조조(C조,n=18)、모형조(M조,n=24)화비낙패특조(F조,n=24).재실험적제4、6、8주시,분별처사1/3적각조대서,관찰각조대서간장지방변성급염증정도,관찰간세포조망정도;검측간조직중PPAR-αmRNA상대표체량급Bcl-2、Bax화Caspase-3 mRNA화단백적표체.다조간비교채용단인소방차분석(one-way ANOVA)법;등급자료채용Kruskal-Wallis H비삼수검험진행분석;상관성분석채용Pearson상관분석화spearman질상관분석량충방법.결과 여C조대서상비,수조모시간적연장,M조대서간세포지방변가중;염증활동도계분승고(1.62±0.92대비0,P＜0.01);간세포조망지수승고(58.86±13.59대비39.55±3.99,P＜0.05),차이균유통계학의의.여C조대서비교,M조대서PPAR mRNA상대표체량강저(0.366±0.068대비0.570±0.061),Bcl-2 mRNA화단백적표체균감저(0.234±0.099대비0.437±0.053화0.0098±0.0002대비0.0155±0.0004),P치균＜0.01,차이균유통계학의의;Bax、Caspase-3 mRNA상대표체량(0.368±0.064대비0.230±0.052화0.363±0.058대비0.218±0.031)화단백표체(0.1311±0.0050대비0.0947±0.0139화0.1297±0.0065대비0.0794±0.0038)균명현증고,P치균＜0.01,차이균유통계학의의.F조대서간세포조망지수강저,간조직PPAR mRNA화Bcl-2 mRNA화단백적상대표체량분별위0.510±0.109、0.425±0.042、0.0148±0.0004,여M조대서비교,P치균＜0.01,차이균유통계학의의;Bax、CaspaSe-3 mRNA화단백상대표체량위0.249±0.034、0.226±0.055、0.0966±0.0069화0.0911±0.0136,여M조대서비교,P치균＜ 0.01,차이균유통계학의의. 결론 비낙패특가감경NAFLD대서간지방변성,기궤제가능여억제NAFLD대서간세포조망유관.
Objective To use a rat model of nonalcoholic liver disease (NAFLD) to observe effects of the peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate on hepatic steatosis in nonalcoholic fatty liver and to investigate the underlying mechanism.Methods Sixty-six SpragueDawley rats were given adaptive feeding for 1 week and then randomly allocated into the following three groups:unmodeled control (group C,n =18),untreated NAFLD model (group M,n =24),and fenofibratetreated NAFLD model (group F,n =24).Group C rats were given a normal diet,while group M and group F rats were given a high-fat diet.After model establishment,the group F rats were treated with fenofibrate (10 mg/kg/d,intraperitoneal) and the group C and group M rats were given sham-treatment with cosolvent (5 mL/kg/d,intraperitoneal).At the end of treatment weeks 4,6 and 8,one-third of rats in each group were euthanized.Liver tissues were assessed by hematoxylin-eosin (HE) staining to determine level of steatosis and inflammaion activity,and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling to measure changes in hepatocyte apoptosis index.Changes in expression levels of the PPAR-α receptor and apoptosis factors (bcl-2,bax and caspase-3) were assessed by reverse transcription-PCR and immunohistochemistry.Results The NAFLD modeled rats showed appropriate induction of hepatic steatosis,hepatic inflammation,and hepatocyte apoptosis.Compared to the group M rats,the group F rats showed lower expression of PPAR-and bcl-2 and higher expression of bax and caspase-3 at both the mRNA and protein level.Conclusion Fenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD,and the mechanism may be associated with inhibition of hepatocyte apoptosis.
