中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2010年
2期
119-123
,共5页
徐新保%何振平%冷希圣%梁志清%彭吉润%张洪义%张宏义%肖梅%张辉%刘承利%张希东
徐新保%何振平%冷希聖%樑誌清%彭吉潤%張洪義%張宏義%肖梅%張輝%劉承利%張希東
서신보%하진평%랭희골%량지청%팽길윤%장홍의%장굉의%초매%장휘%류승리%장희동
肝硬化%癌,肝细胞%小鼠%转化生长因子β1%Smad4基因
肝硬化%癌,肝細胞%小鼠%轉化生長因子β1%Smad4基因
간경화%암,간세포%소서%전화생장인자β1%Smad4기인
Liver cirrhosis Carcinoma,hepatocellular%Mice%Transforming growth factor beta%Smad4 gene
目的 探讨敲除Smad4基因对转化生长因子β1(TGFβ1)信号传导系统和对肝纤维化及肝癌发生和发展的影响.方法 采用CCl_4/乙醇分别诱导野生型小鼠(Smad4+/+)与Smad4基因敲除小鼠 (Smad4+/-)20周,观察每组小鼠发生肝纤维化和肝癌的情况,并采用RT-PCR方法检测Smad4、TGFβ1、Smad2、Smad3、Smad6,基质金属蛋白酶抑制剂1、基质金属蛋白酶2、9等基因的mRNA表达程度.采用χ~2检验与t检验进行统计学处理. 结果 纤维化肝脏Smad4的表达较正常对照组明显增强.与野生型相比,Smad4杂合子小鼠的TGFβ1-Smads信号传导系统有所减弱.经CCl_4/乙醇诱导后,总体上Smad4杂合子小鼠发生肝纤维化的程度 (评分为2.12±0.88)显著低于野生型小鼠 (评分为2.87±0.88,t=3.163,P=0.003);Smad4杂合子小鼠组的肝癌发生率 (32.0%) 也明显低于野生型小鼠组 (41.9%).结论 敲除Smad4基因能有效弱化TGFβ1信号传导,从而减缓肝纤维化的程度;同时,能减缓肝癌的发展进程.
目的 探討敲除Smad4基因對轉化生長因子β1(TGFβ1)信號傳導繫統和對肝纖維化及肝癌髮生和髮展的影響.方法 採用CCl_4/乙醇分彆誘導野生型小鼠(Smad4+/+)與Smad4基因敲除小鼠 (Smad4+/-)20週,觀察每組小鼠髮生肝纖維化和肝癌的情況,併採用RT-PCR方法檢測Smad4、TGFβ1、Smad2、Smad3、Smad6,基質金屬蛋白酶抑製劑1、基質金屬蛋白酶2、9等基因的mRNA錶達程度.採用χ~2檢驗與t檢驗進行統計學處理. 結果 纖維化肝髒Smad4的錶達較正常對照組明顯增彊.與野生型相比,Smad4雜閤子小鼠的TGFβ1-Smads信號傳導繫統有所減弱.經CCl_4/乙醇誘導後,總體上Smad4雜閤子小鼠髮生肝纖維化的程度 (評分為2.12±0.88)顯著低于野生型小鼠 (評分為2.87±0.88,t=3.163,P=0.003);Smad4雜閤子小鼠組的肝癌髮生率 (32.0%) 也明顯低于野生型小鼠組 (41.9%).結論 敲除Smad4基因能有效弱化TGFβ1信號傳導,從而減緩肝纖維化的程度;同時,能減緩肝癌的髮展進程.
목적 탐토고제Smad4기인대전화생장인자β1(TGFβ1)신호전도계통화대간섬유화급간암발생화발전적영향.방법 채용CCl_4/을순분별유도야생형소서(Smad4+/+)여Smad4기인고제소서 (Smad4+/-)20주,관찰매조소서발생간섬유화화간암적정황,병채용RT-PCR방법검측Smad4、TGFβ1、Smad2、Smad3、Smad6,기질금속단백매억제제1、기질금속단백매2、9등기인적mRNA표체정도.채용χ~2검험여t검험진행통계학처리. 결과 섬유화간장Smad4적표체교정상대조조명현증강.여야생형상비,Smad4잡합자소서적TGFβ1-Smads신호전도계통유소감약.경CCl_4/을순유도후,총체상Smad4잡합자소서발생간섬유화적정도 (평분위2.12±0.88)현저저우야생형소서 (평분위2.87±0.88,t=3.163,P=0.003);Smad4잡합자소서조적간암발생솔 (32.0%) 야명현저우야생형소서조 (41.9%).결론 고제Smad4기인능유효약화TGFβ1신호전도,종이감완간섬유화적정도;동시,능감완간암적발전진정.
Objective To study the effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl_4/ethanol. Methods The wild-type mice (Smad4 +/+) and the Smad4 knockout mice (Smad4 +/-) were injected subcutaneously with carbon tetrachloride(CCl_4)/ethanol twice a week for twenty weeks. The expression of Smad4, TGF β1, Smad2, Smad3, Smad6, TIMP1, MMP2 and MMP9 was detected by RT-PCR. Results In the cirrhotic liver, the expression of Smad4 mRNA was significantly higher than that in the normal liver. Comparing with wild-type mice (Smad4 +/+), the TGF β 1-Smad4 signaling was mark-edly attenuated in the Smad4 knockout mice (Smad4 +/-). After induction by CCl_4)/ethanol, the hepatic fibro-sis in the Smad4 knockout mice (Smad4 +/-) was obviously alleviated compared with the wild-type mice (Smad4 +/+), and the incidence rate of hepatocarcinogenesis of the former was also lower than that of the latter(32.0% vs 41.9%). Conclusion These results indicate that knocking out Smad4 can delay the progres-sion of liver fibrosis and liver cancer.
