中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2014年
10期
784-787
,共4页
胡辉%荆绪斌%邹细岩%吴锦雄
鬍輝%荊緒斌%鄒細巖%吳錦雄
호휘%형서빈%추세암%오금웅
环氧化酶2抑制剂%肝星形细胞%细胞周期蛋白类%肝纤维化
環氧化酶2抑製劑%肝星形細胞%細胞週期蛋白類%肝纖維化
배양화매2억제제%간성형세포%세포주기단백류%간섬유화
Cyclooxygenase 2 inhibitors%Hepatic stellate cells%Cyclins%Liver cirrhosis
目的 探讨环氧化酶2 (COX-2)及其抑制剂代他考昔在小鼠肝纤维化中的作用.方法 选取6～8周成年雄性野生型小鼠或COX-2基因敲除小鼠共35只,其中5只野生型小鼠腹腔注射1 ml/kg橄榄油为对照组,另外野生型小鼠及COX-2基因敲除小鼠各15只腹腔注射1ml/kg溶解于橄榄油的20％四氯化碳作为野生型实验组和基因敲除实验组.8周后检测各组小鼠肝组织病理改变以及血清透明质酸(HA)、Ⅳ型胶原(Ⅳ-C),Ⅲ型前胶原(PCⅢ)及α平滑肌肌动蛋白(α-SMA)的表达；分离各实验组小鼠肝星形细胞,COX-2抑制剂代他考昔100 μmol/L作用肝星形细胞24 h后,检测药物作用前后细胞周期蛋白(cyclin)D、E表达的情况.结果 总体各组小鼠HA、Ⅳ-C、PCⅢ、α-SMA表达差异均有统计学意义[对照组分别为:(180±13)μg/L、(56 ±9)μg/L、(39±13) μg/L、2.49％±0.24％,F=78.52、61.30、41.96、28.15,均P＜0.05].野生型实验组小鼠血清HA、Ⅳ-C、α-SMA含量均高于基因敲除实验组(413±60)比(308±42) μg/L、(96±13)比(74±10)μg/L,8.99％ ±0.81％比4.72％ ±0.50％,均P＜0.05),两组PCⅢ差异无统计学意义[(82±12)比(72±15) μg/L,P=0.06].野生型实验组肝星形细胞cyclin D、cyclin E表达均高于基因敲除组(0.96 ±0.15比0.76±0.10、0.94±0.13比0.82±0.09,P=0.02、0.04)；代他考昔作用后野生型实验组及基因敲除实验组小鼠cyclin D、E则分别为(0.40 ±0.06、0.38±0.05,0.35 ±0.04、0.37±0.06),均明显低于未用药前(均P＜0.01).结论 COX-2能引起肝星形细胞活化、增殖导致肝纤维化；COX-2抑制剂能通过COX-2依赖途径和COX-2非依赖途径下调肝星形细胞cyclin D、cyclin E表达发挥抗纤维化作用.
目的 探討環氧化酶2 (COX-2)及其抑製劑代他攷昔在小鼠肝纖維化中的作用.方法 選取6～8週成年雄性野生型小鼠或COX-2基因敲除小鼠共35隻,其中5隻野生型小鼠腹腔註射1 ml/kg橄欖油為對照組,另外野生型小鼠及COX-2基因敲除小鼠各15隻腹腔註射1ml/kg溶解于橄欖油的20％四氯化碳作為野生型實驗組和基因敲除實驗組.8週後檢測各組小鼠肝組織病理改變以及血清透明質痠(HA)、Ⅳ型膠原(Ⅳ-C),Ⅲ型前膠原(PCⅢ)及α平滑肌肌動蛋白(α-SMA)的錶達；分離各實驗組小鼠肝星形細胞,COX-2抑製劑代他攷昔100 μmol/L作用肝星形細胞24 h後,檢測藥物作用前後細胞週期蛋白(cyclin)D、E錶達的情況.結果 總體各組小鼠HA、Ⅳ-C、PCⅢ、α-SMA錶達差異均有統計學意義[對照組分彆為:(180±13)μg/L、(56 ±9)μg/L、(39±13) μg/L、2.49％±0.24％,F=78.52、61.30、41.96、28.15,均P＜0.05].野生型實驗組小鼠血清HA、Ⅳ-C、α-SMA含量均高于基因敲除實驗組(413±60)比(308±42) μg/L、(96±13)比(74±10)μg/L,8.99％ ±0.81％比4.72％ ±0.50％,均P＜0.05),兩組PCⅢ差異無統計學意義[(82±12)比(72±15) μg/L,P=0.06].野生型實驗組肝星形細胞cyclin D、cyclin E錶達均高于基因敲除組(0.96 ±0.15比0.76±0.10、0.94±0.13比0.82±0.09,P=0.02、0.04)；代他攷昔作用後野生型實驗組及基因敲除實驗組小鼠cyclin D、E則分彆為(0.40 ±0.06、0.38±0.05,0.35 ±0.04、0.37±0.06),均明顯低于未用藥前(均P＜0.01).結論 COX-2能引起肝星形細胞活化、增殖導緻肝纖維化；COX-2抑製劑能通過COX-2依賴途徑和COX-2非依賴途徑下調肝星形細胞cyclin D、cyclin E錶達髮揮抗纖維化作用.
목적 탐토배양화매2 (COX-2)급기억제제대타고석재소서간섬유화중적작용.방법 선취6～8주성년웅성야생형소서혹COX-2기인고제소서공35지,기중5지야생형소서복강주사1 ml/kg감람유위대조조,령외야생형소서급COX-2기인고제소서각15지복강주사1ml/kg용해우감람유적20％사록화탄작위야생형실험조화기인고제실험조.8주후검측각조소서간조직병리개변이급혈청투명질산(HA)、Ⅳ형효원(Ⅳ-C),Ⅲ형전효원(PCⅢ)급α평활기기동단백(α-SMA)적표체；분리각실험조소서간성형세포,COX-2억제제대타고석100 μmol/L작용간성형세포24 h후,검측약물작용전후세포주기단백(cyclin)D、E표체적정황.결과 총체각조소서HA、Ⅳ-C、PCⅢ、α-SMA표체차이균유통계학의의[대조조분별위:(180±13)μg/L、(56 ±9)μg/L、(39±13) μg/L、2.49％±0.24％,F=78.52、61.30、41.96、28.15,균P＜0.05].야생형실험조소서혈청HA、Ⅳ-C、α-SMA함량균고우기인고제실험조(413±60)비(308±42) μg/L、(96±13)비(74±10)μg/L,8.99％ ±0.81％비4.72％ ±0.50％,균P＜0.05),량조PCⅢ차이무통계학의의[(82±12)비(72±15) μg/L,P=0.06].야생형실험조간성형세포cyclin D、cyclin E표체균고우기인고제조(0.96 ±0.15비0.76±0.10、0.94±0.13비0.82±0.09,P=0.02、0.04)；대타고석작용후야생형실험조급기인고제실험조소서cyclin D、E칙분별위(0.40 ±0.06、0.38±0.05,0.35 ±0.04、0.37±0.06),균명현저우미용약전(균P＜0.01).결론 COX-2능인기간성형세포활화、증식도치간섬유화；COX-2억제제능통과COX-2의뢰도경화COX-2비의뢰도경하조간성형세포cyclin D、cyclin E표체발휘항섬유화작용.
Objective To explore the effects of cyclooxygenase-2 (COX-2) and its inhibitor valdecoxib in liver fibrosis.Methods Hepatic fibrosis was induced by carbon tetrachloride for 8 weeks in wild-type and COX-2 knockout mice.And the levels of hyaluronic acid (HA),collagen Ⅳ (Ⅳ-C),procollagen Ⅲ (PC Ⅲ) and a-smooth muscle actin (α-SMA) were determined.Cyclin D and cyclin E were measured in hepatic satellite cell (HSC) after a treatment of valdecoxib for 24 h or not.Results HA,Ⅳ-C,PC Ⅲ and α-SMA all had significant difference in 3 groups (control group:(180 ± 13)μg/L,(56 ± 9) μg/L,(39 ±13)μg/L,2.49％ ±0.24％ in control,F=78.52,61.30,41.96,28.15,all P＜0.05).HA,Ⅳ-C and α-SMA in wild-type liver fibrosis mice were higher than those in knockout counterparts ((413±60) vs (308 ±42)μg/L,(96±13) vs (74±10)μg/L,8.99％ ±0.81％ vs4.72％ ±0.50％,all P ＜ 0.01).But PC Ⅲ were similar between two groups ((82 ± 12) vs (72 ± 15) μg/L,P =0.06).Wild-type mice expressed higher levels of cyclin D and cyclin E than those of knockout mice (0.96 ± 0.15 vs 0.76 ± 0.10,0.94±0.13 vs0.82±0.09,P=0.02,0.04).The rates of cyclin DandcyclinEwere 0.40 ±0.06 and 0.38 ± 0.05,0.35 ± 0.04 and 0.37 ± 0.06 respectively after a treatment of valdecoxib.And both deceased in hepatic satellite cell of wild-type and knockout mice (both P ＜ 0.01) versus those without valdecoxib.Conclusions COX-2 increases the activation and proliferation of HSC leading to liver fibrosis.And its inhibitor may depress liver fibrosis by decreasing the expressions of cyclin D and cyclin E in COX-2 dependent and(or) independent way.
