中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2015年
2期
124-129
,共6页
史婷婷%庄让笑%周红萍%王福根%邵益丹%蔡兆斌
史婷婷%莊讓笑%週紅萍%王福根%邵益丹%蔡兆斌
사정정%장양소%주홍평%왕복근%소익단%채조빈
芹菜素%肝炎,脂肪性,非酒精性%过氧化物酶体增殖物激活受体%PPARα/γ双重激动剂
芹菜素%肝炎,脂肪性,非酒精性%過氧化物酶體增殖物激活受體%PPARα/γ雙重激動劑
근채소%간염,지방성,비주정성%과양화물매체증식물격활수체%PPARα/γ쌍중격동제
Apigenin%Nonalcoholic steatohepatitis%Peroxisome proliferator-activated receptors%PPARγ/PPARα dual agonists
目的 探讨芹菜素对非酒精性脂肪性肝炎(NASH)大鼠肝组织过氧化物酶体增殖物激活受体(PPARs)表达的影响. 方法 采用高脂饲料喂养的方法复制大鼠NASH模型,成模后分为正常组,模型组,多烯磷脂酰胆碱组,芹菜素低剂量组、中剂量组和高剂量组.实验结束后,进行胰岛素敏感性测定;腹腔静脉取血测定生物化学指标ALT、AST、总胆固醇(TC)、总甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)和空腹胰岛素(FINS);计算肝指数和胰岛素抵抗指数(HOMA-IR);提取肝组织,运用免疫组织化学和RT-PCR测定各组大鼠肝组织PPAR α 、PPAR γ蛋白和mRNA表达情况.多组间的比较采用单因素方差分析.结果 胰岛素敏感性的变化:各组之间差异均有统计学意义,两两比较结果显示,正常组明显高于其他组,而芹菜素组高于模型组,尤其是高剂量组;生物化学指标检测结果显示:与模型组ALT[(163.1±15.5) U/L、AST (284.6±23.5) U/L]活性和TC[(2.23±0.76)mmol/L]、TG[(1.94±0.33) mmol/L]、LDL-C[(2.63±0.18) mmol/L]、HDL-C[(0.77±0.51)mmol/L]、FBG[(8.64±1.02) mmol/L]和FINS[(3.48±1.41) U/L]含量相比,芹菜素组尤其是高剂量组能减少ALT [(95.4±7.3)U/L]、AST [(183.7±14.3)U/L]活性和TC [(1.61±0.25)mmol/L]、TG[(1.23土0.21) mmol/L、LDL-C[(1.86±0.13) mmol/L、FBG[(5.29±1.45)mmol/L和FINS[(0.76±0.86) U/L]的含量,升高HDL-C[(1.04±0.17) mmol/L]的含量;与模型组大鼠肝指数(3.75±0.25)和HOMA-IR (1.34±0.06)相比,芹菜素组尤其是高剂量组能够显著减低肝指数(2.90±0.17)和HOMA-IR(0.18土0.04,P＜0.05);免疫组织化学染色和RT-PCR结果显示:与模型组相比,芹菜素组PPAR α 、PPARγ蛋白和mRNA表达增加,尤其是高剂量组,PPAR α 蛋白和mRNA相对表达量分别为18.27±4.05和0.63±0.02,PPAR γ蛋白和mRNA相对表达量分别为8.48±5.05和0.39±0.02,P＜0.05. 结论 芹菜素能改善胰岛素抵抗和糖脂代谢,减轻肝脏脂肪变性和炎症坏死,降低血清TC、TG、LDL-C、FBG、FINS和HOMA-IR水平,提高HDL-C水平,推测其可能对大鼠NASH具有保护作用.
目的 探討芹菜素對非酒精性脂肪性肝炎(NASH)大鼠肝組織過氧化物酶體增殖物激活受體(PPARs)錶達的影響. 方法 採用高脂飼料餵養的方法複製大鼠NASH模型,成模後分為正常組,模型組,多烯燐脂酰膽堿組,芹菜素低劑量組、中劑量組和高劑量組.實驗結束後,進行胰島素敏感性測定;腹腔靜脈取血測定生物化學指標ALT、AST、總膽固醇(TC)、總甘油三酯(TG)和低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)、空腹血糖(FBG)和空腹胰島素(FINS);計算肝指數和胰島素牴抗指數(HOMA-IR);提取肝組織,運用免疫組織化學和RT-PCR測定各組大鼠肝組織PPAR α 、PPAR γ蛋白和mRNA錶達情況.多組間的比較採用單因素方差分析.結果 胰島素敏感性的變化:各組之間差異均有統計學意義,兩兩比較結果顯示,正常組明顯高于其他組,而芹菜素組高于模型組,尤其是高劑量組;生物化學指標檢測結果顯示:與模型組ALT[(163.1±15.5) U/L、AST (284.6±23.5) U/L]活性和TC[(2.23±0.76)mmol/L]、TG[(1.94±0.33) mmol/L]、LDL-C[(2.63±0.18) mmol/L]、HDL-C[(0.77±0.51)mmol/L]、FBG[(8.64±1.02) mmol/L]和FINS[(3.48±1.41) U/L]含量相比,芹菜素組尤其是高劑量組能減少ALT [(95.4±7.3)U/L]、AST [(183.7±14.3)U/L]活性和TC [(1.61±0.25)mmol/L]、TG[(1.23土0.21) mmol/L、LDL-C[(1.86±0.13) mmol/L、FBG[(5.29±1.45)mmol/L和FINS[(0.76±0.86) U/L]的含量,升高HDL-C[(1.04±0.17) mmol/L]的含量;與模型組大鼠肝指數(3.75±0.25)和HOMA-IR (1.34±0.06)相比,芹菜素組尤其是高劑量組能夠顯著減低肝指數(2.90±0.17)和HOMA-IR(0.18土0.04,P＜0.05);免疫組織化學染色和RT-PCR結果顯示:與模型組相比,芹菜素組PPAR α 、PPARγ蛋白和mRNA錶達增加,尤其是高劑量組,PPAR α 蛋白和mRNA相對錶達量分彆為18.27±4.05和0.63±0.02,PPAR γ蛋白和mRNA相對錶達量分彆為8.48±5.05和0.39±0.02,P＜0.05. 結論 芹菜素能改善胰島素牴抗和糖脂代謝,減輕肝髒脂肪變性和炎癥壞死,降低血清TC、TG、LDL-C、FBG、FINS和HOMA-IR水平,提高HDL-C水平,推測其可能對大鼠NASH具有保護作用.
목적 탐토근채소대비주정성지방성간염(NASH)대서간조직과양화물매체증식물격활수체(PPARs)표체적영향. 방법 채용고지사료위양적방법복제대서NASH모형,성모후분위정상조,모형조,다희린지선담감조,근채소저제량조、중제량조화고제량조.실험결속후,진행이도소민감성측정;복강정맥취혈측정생물화학지표ALT、AST、총담고순(TC)、총감유삼지(TG)화저밀도지단백담고순(LDL-C)、고밀도지단백담고순(HDL-C)、공복혈당(FBG)화공복이도소(FINS);계산간지수화이도소저항지수(HOMA-IR);제취간조직,운용면역조직화학화RT-PCR측정각조대서간조직PPAR α 、PPAR γ단백화mRNA표체정황.다조간적비교채용단인소방차분석.결과 이도소민감성적변화:각조지간차이균유통계학의의,량량비교결과현시,정상조명현고우기타조,이근채소조고우모형조,우기시고제량조;생물화학지표검측결과현시:여모형조ALT[(163.1±15.5) U/L、AST (284.6±23.5) U/L]활성화TC[(2.23±0.76)mmol/L]、TG[(1.94±0.33) mmol/L]、LDL-C[(2.63±0.18) mmol/L]、HDL-C[(0.77±0.51)mmol/L]、FBG[(8.64±1.02) mmol/L]화FINS[(3.48±1.41) U/L]함량상비,근채소조우기시고제량조능감소ALT [(95.4±7.3)U/L]、AST [(183.7±14.3)U/L]활성화TC [(1.61±0.25)mmol/L]、TG[(1.23토0.21) mmol/L、LDL-C[(1.86±0.13) mmol/L、FBG[(5.29±1.45)mmol/L화FINS[(0.76±0.86) U/L]적함량,승고HDL-C[(1.04±0.17) mmol/L]적함량;여모형조대서간지수(3.75±0.25)화HOMA-IR (1.34±0.06)상비,근채소조우기시고제량조능구현저감저간지수(2.90±0.17)화HOMA-IR(0.18토0.04,P＜0.05);면역조직화학염색화RT-PCR결과현시:여모형조상비,근채소조PPAR α 、PPARγ단백화mRNA표체증가,우기시고제량조,PPAR α 단백화mRNA상대표체량분별위18.27±4.05화0.63±0.02,PPAR γ단백화mRNA상대표체량분별위8.48±5.05화0.39±0.02,P＜0.05. 결론 근채소능개선이도소저항화당지대사,감경간장지방변성화염증배사,강저혈청TC、TG、LDL-C、FBG、FINS화HOMA-IR수평,제고HDL-C수평,추측기가능대대서NASH구유보호작용.
Objective To investigate the effect of apigenin on the protein expression levels of peroxisome proliferator-activated receptors (PPARs) in liver tissues of rats with nonalcoholic steatohepatitis (NASH).Methods The NASH rat model was established by feeding of a high-fat diet.Unmodeled rats served as the normal controls.The modeled rats were divided into a model control group,Essentiale treatment group (300 mg/kg/day),and three apigenin treatment groups for low-dose (15 mg/kg/day),moderate-dose (30 mg/kg/day) and high-dose (60 mg/kg/day).After 13 weeks of treatment,changes in insulin sensitivity from pre-treatment baseline were assessed by measuring the alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglycerides (TG),low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C),fasting blood glucose (FBG) and fasting insulin (FINS).The liver index and HOMA-IR were also calculated.Protein and gene expression of PPARa and PPARγ in liver tissue were assessed by immunohistochemistry and RT-PCR.Statistical analysis was performed by the LSD test and Games-Howell test.Results The apigenintreated groups showed a significantly greater change in insulin sensitivity than the untreated model group,with the most significant change occurring in the high-dose group (P ＜ 0.05).Compared with the untreated model group,the apigenin-treated groups showed lower levels of ALT (95.4±7.3),AST (183.7±14.3),TC (1.61±0.25),TG (1.23±0.21),LDL-C (1.86±0.14),FBG (5.29±1.45) and FINS (0.76±0.86),but a higher level of HDL-C (1.04±0.17); again,the high-dose group showed the greatest change (all P ＜ 0.05).Compared to the untreated model group,the apigenin-treated groups showed significantly lower liver index (3.75±0.25 vs.2.90±0.17) and HOMA-IR (1.34±0.06 vs.0.18±0.04),with the high-dose group showing the greatest change (both P ＜ 0.05).Compared to the untreated model group,the apigenin-treated groups showed higher levels of protein and mRNA of PPARα (18.27±4.05 and 0.63±0.02,respectively) and PPARγ(8.48±5.05 and 0.39±0.02),with the high-dose group showing the greatest change (all P ＜ 0.05).Conclusion Apigenin can improve glucose tolerance,lipid metabolism and insulin resistance while decreasing blood levels of TC,TG,LDL-C,FBG,FINS and HOMA-IR,and increasing HDL-C in NASH,as shown in a high-fat diet induced rat model,and may have therapeutic potential.
