Smad4和TGF-βRⅡ在肝细胞癌中的表达及意义

目的探讨转化生长因子β(TGF-β)通路中Smad4蛋白与转化生长因子βⅡ型受体(TGF-β RⅡ)蛋白的变化及其在肝细胞癌中可能的作用机制.方法用免疫组化SABC法检测45例石蜡包埋人肝细胞癌标本及36例癌旁组织中Smad4、TGF-β RⅡ蛋白表达情况.结果 45例肝癌组织中,Smad4、TGF-βRⅡ阳性表达率分别为51.5%和42.2%.肝细胞癌组织中Smad4、TGF-β RⅡ阳性表达与癌旁组织比较均明显降低(P＜0.05),且与包膜是否完整和有无癌栓有关(P＜0.05),TGF-βRⅡ与肝细胞癌组织分化程度有相关性(P＜0.05).结论肝细胞癌组织中Smad4、TGF-β RⅡ阳性表达均降低,Smad4及TGF-β RⅡ的丢失、功能失活对诱发肝细胞癌及肝细胞转移都起到一定作用.     

乳腺癌组织中MMP-2、TIMP-2、TGF-β1、TGF-β1 RⅠ的表达及相关性分析

目的 探讨基质金属蛋白酶(MMP)-2及其抑制物(TIMP-2)与转化生长因子(TGF)-β1及其Ⅰ型受体(TGF-β1RⅠ)在乳腺癌组织中的表达及其相关性.方法 应用免疫组化SP法检测80例乳腺癌组织中的MMP-2、TIMP-2与TGF-β1、TGF-β1RⅠ蛋白.结果 乳腺癌中MMP-2、TIMP-2、TGF-β1和TGF-β1RⅠ阳性表达率分别为67.5%、45.0%、80.0%和67.5%;无淋巴结转移者MMP-2、TIMP-2阳性表达率为44.4%、66.7%,与转移淋巴结个数1～3(85.7%、21.4%)、＞3个(87.5%、37.5%)相比,P均＜0.01;TNM分期为Ⅰ期的MMP-2、TIMP-2阳性表达率分别为0、75%,分别与Ⅱ(65.0%、55.0%)、Ⅲ(86.7%、26.7%)、Ⅳ期(100%、0)相比,P均＜0.05;肿瘤直径≤2 cm者TIMP-2阳性表达率为66.7%,与直径2～5(51.9%)、＞5 cm(20.0%)相比,P均＜0.05;MMP-2和TGF-β1的表达呈正相关(r=0.454,P＜0.01),MMP-2和TGF-β1RⅠ的表达呈负相关(r=-0.481,P＜0.01).结论 MMP-2和TIMP-2的表达情况与乳腺癌侵袭转移有密切关系.MMP-2的表达与TGF-β1、TGF-β1RⅠ关系密切,MMP-2可能在一定程度上受到TGF-β1及其受体的调控.     

胃癌及癌前病变组织中转化生长因子β工型受体的表达与细胞凋亡

目的探讨胃癌及癌前病变中转化生长因子βⅠ型受体(TGF-βRⅠ)的表达与细胞凋亡的关系及它们在胃癌发病机制中的作用.方法免疫组化SP法检测慢性浅表性胃炎(30例)、肠化生(30例)、不典型增生(18例)及胃癌(25例)中TGF-βRⅠ的表达,TUNEL法检测其中凋亡细胞的情况.结果从慢性浅表性胃炎到肠化生、不典型增生及胃癌,TGF-βRⅠ表达及凋亡指数(AI)分级均与胃粘膜病变程度显著负相关(分别为r=-0.7272,P＜0.01;r=-0.8347,P＜0.01),19例胃癌(76%)TGF-βRⅠ表达缺失;不同组织学类型中AI的分布和TGF-βRⅠ表达的分布差异无显著性(P=0.0779).结论TGF-βRⅠ表达缺失可能影响细胞凋亡,参与胃癌的发生.     

转化生长因子β1在人肝纤维化组织中的表达及作用的探讨

目的:探讨转化生长因子β1(TGF-β1)在人肝纤维化组织中的分布和作用.方法:采用放射免疫方法检测36例慢性乙型肝炎患者血清中PCⅢ、Ⅳ-C、HA、LN水平,同时采用原位杂交和免疫组化的方法检测其肝组织中TGF-51mRNA及蛋白表达情况,并对蛋白表达结果进行半定量分析.结果:TGF-β1mRNA和蛋白表达于肝纤维化活跃的汇管区、纤维间隔、Disse间隙及肝细胞变性坏死处,随肝纤维化程度的加重,TGF-β1蛋白表达着色积分增加(S0期1.4±0.8,S1期1.7±0.9,S2期2.9±1.0,S3期4.8±1.5,S4期6.8±1.5);并且与血清PCⅢ,Ⅳ-C,HA及LN水平呈明显的正相关(r=0.39,P＜0.05;r=0.436,P＜0.05;r=0.63,P＜0.01;r=0.40,P＜0.05).结论:TGF-β1与胶原蛋白沉积密切相关,在人肝纤维化的形成和发展中起关键性的作用.     

肝组织内性甾体激素受体与慢性乙型肝炎病毒复制及其抗原表达的相关性

目的：探讨肝组织内雄激素受体（AR）和雌激素受体-α（ERα）含量对慢性乙型肝炎（CHB）患者血清 HBV DNA载量、HBsAg水平和肝组织内 HBsAg、HBcAg表达水平影响。方法135例经肝活组织检查的CHB患者入选本研究,其中 HBeAg阳性80例,HBeAg阴性55例。肝组织内AR mRNA和ERαmRNA采用反转录定量PCR检测。结果 HBeAg阳性患者,血清HBV DNA载量与肝组织内AR mRNA和ERαmRNA含量均无显著相关性（r＝0．132,P＝0．241和r＝0．130,P＝0．249）,血清 HBsAg 水平与肝组织内 AR mRNA 和 ERαmRNA 含量均呈显著正相关（r＝0．355,P＝0．001和r＝0．246,P＝0．028）;肝组织内 HBcAg 表达水平与肝组织内AR mRNA和 ERαmRNA 含量均呈显著正相关（rs＝0．438,P＝0．000和rs＝0．352,P＝0．002）,肝组织内 HBsAg 表达水平与肝组织内AR mRNA和ERαmRNA含量无显著相关性（rs＝0．112,P＝0．333和rs＝0．024,P＝0．836）。HBeAg 阴性患者,血清 HBV DNA载量与肝组织内AR mRNA和ERαmRNA含量均无显著相关性（r＝-0．256,P＝0．061和r＝-0．121,P＝0．385）,血清HBsAg水平与肝组织内AR mRNA和ERαmRNA含量均无显著相关性（r＝0．130,P＝0．348和r＝0．165,P＝0．234）;肝组织内 HBcAg表达水平与肝组织内AR mRNA和ERαmRNA含量均无显著相关性（rs＝-0．053,P＝0．701和rs＝-0．203,P＝0．137）,肝组织内 HBsAg表达水平与肝组织内AR mRNA和ERαmRNA含量无显著相关性（rs＝0．159, P＝0．247和rs＝0．192,P＝0．160）。多因素方差分析和有序Logistic 回归分析的结果显示,肝组织内AR mRNA 为影响HBeAg阳性患者血清 HBsAg水平和肝组织内 HBcAg表达水平的独立因素。结论肝组织内AR表达水平是影响CHB患者 HBV抗原表达的一个独立因素。     

溃疡性结肠炎患者结肠黏膜转化生长因子-β1及其受体表达与临床病理因素的相关性

背景：转化生长因子（TGF）-β1是溃疡性结肠炎（UC）的一种重要抗炎因子,目前TGF-β1及其Ⅰ型受体（TGFβRⅠ）在UC中表达状况的研究仍较少。目的：探讨TGF-β1、TGFβRⅠ在UC结肠黏膜中的表达及其与临床病理因素的关系。方法：以免疫组化SABC法检测60例UC患者结肠黏膜中TGF-β1、TGFβRⅠ的表达,设16例正常结肠组织作为对照。分析TGF-β1、TGFβRⅠ的表达与病变范围和组织病理学分级的关系。结果：TGF-β1、TGFβRⅠ在UC中的表达显著强于正常对照组（P〈0.05）,且活动期显著强于缓解期（P〈0.05）。TGF-β1、TGFβRⅠ与组织病理学分级均呈正相关（rs分别为0.421和0.553,P〈0.05）,与病变范围均不相关（rs分别为-0.031和-0.037,P〉0.05）。结论：UC结肠黏膜中TGF-β1和TGFβRⅠ表达增强,与UC的发病机制密切相关,有可能成为反映UC疾病活动度的生物学指标。     

转化生长因子β1在慢性乙型肝炎患者肝细胞损伤和肝纤维化形成中的意义

目的 观察慢性乙型肝炎(CHB)、肝硬化(LC)患者血清转化生长因子-β1(TGF-β1)与肝细胞损伤、肝脏纤维组织增生的关系.方法 采用酶联免疫吸附试验(ELISA)测定76例CHB、LC患者血清TGF-β1.肝活检29例,应用多媒体彩色图文分析系统对肝内胶原纤维、网状纤维进行定量分析.结果 (1)CHB轻、中、重度、LC患者血清TGF-β1水平分别为(144.3±57.1)mg/L、(394.5±107.7)mg/L、(508.3±133.3)mg/L、(579.4±225.1)mg/L.依次升高(P＜0.01或P＜0.05);明显高于对照组(95.3±34.1)mg/L(P＜0.01).(2)血清TGF-β1与Ⅲ型前胶原蛋白(PCⅢ)、层粘连蛋白(LN)、透明质酸(HA)呈正相关(P＜0.01或P＜0.05);血清TGF-β1升高与肝组织纤维化程度的加重、肝组织内胶原纤维、网状纤维含量的增长呈同步性(P＜0.01或P＜0.05).(3)ALT＞160U/L组、SB＞85.5μmol/L组血清TGF-β1水平明显高于肝功能轻度异常和正常组(P＜0.01或P＜0.05).结论 TGF-β1在CHB肝纤维化的发病机制中起着不可忽视的作用,血清TGF-β1的检测可用于CHB肝纤维化程度和肝细胞受损程度的判断.     

肝癌组织中TGF-β1、TGF-β1RⅡ和NF-κB的表达

目的:探讨转化生长因子β1(TGF-β1)、转化生长因子β1Ⅱ型受体(TGF-β1RⅡ)、核转录因子-κB(NF-κB)在肝细胞癌(HCC)中表达.方法:在30例肝癌组织和癌旁肝组织中,用免疫组化技术,分别检测TGF-β1 TGF-β1RⅡ及NF-κB蛋白的表达;用原位杂交方法检测TGF-β1mRNA的表达,以CD34标记血管内皮细胞,观察TGF-β1及TGF-β1RⅡ蛋白与微血管密度(MVD)、TGF-β1蛋白与TGF-β1mRNA、NF-κB与TGF-β1的关系.结果:肝癌组织TGF-β1mRNA平均光密度明显高于癌旁组织(0.1 043±0.035 vs 0.0 620±0.0 225,P＜0.01)、TGF-β1蛋白平均光密度表达明显高于癌旁组织(0.0 72 5±0.0 102 vs 0.0 442±0.0 103,P＜0.01);肝癌组织TGF-β1RⅡ蛋白平均光密度表达明显低于癌旁组织(0.0 402±0.0 113 vs 0.0 669±0.0 157,P＜0.01);肝癌组织NF-KB蛋白表达均明显高于癌旁组织(0.0 723±0.0 210 vs 0.0 305±0.0116,P＜0.01),肝癌组织MVD明显高于癌旁组织(31.23±9.25 vs 4.24±2.10,P＜0.01),肝癌组织TGF-β1蛋白阳性表达与MVD呈正相关(t=3.25,P＜0.01);TGF-β1 mRNA与TGF-β1蛋白呈正相关(χ2=8.21,P＜0.01);NF-κB蛋白阳性表达与TGF-β1蛋白阳性表达呈正相关(χ2=9.075,P＜0.01);而TGF-βRⅡ蛋白与MVD呈负相关.结论:肝癌组织中TGF-β1基因的变化发生在多个水平,肝癌细胞中TGF-β1RⅡ、NF-KB蛋白表达异常,并与MVD相关,提示他们在肝细胞癌血管形成中发挥重要作用,NF-κB可能在介导TGF-β1的活化或产生中发挥一定的作用.     

五灵胶囊对肝纤维化大鼠肝组织TGF-β／Smad及Ras／ERK信号通路蛋白的影响

目的探讨五灵胶囊对肝纤维化大鼠肝组织TGF-βSmad及Ras／ERK信号通路蛋白的影响,阐述五灵胶囊治疗肝纤维化的作用机制。方法SD大鼠以高脂低蛋白饲料饲养,饮用10％乙醇,并腹腔注射4．1mol／LCCl4制备肝纤维化模型,给予五灵胶囊进行治疗1个月。Westernblot检测肝组织中α-SMA、Ras、ERK、p-ERK、Smad2／3、p-Smad2／3、Smad7、TJ3RI、T13R1I;RT-PCR法检测肝组织中COL-Ⅰ、COL-Ⅲ、TGF-β1mRNA;酶法测定血清ALT、AST;ELISA测定血清COL-Ⅰ、COL-Ⅲ含量;肝组织masson和HE染色进行肝细胞变性程度与胶原纤维增生程度评分。结果五灵胶囊可显著降低血清AST、ALT水平,下调肝组织中Rasp21、α-SMA、p-ERK、T13RI蛋白与TGF-β1、COL-I、COL-Ⅲ mRNA表达（P〈0．01或0．05）,增加p-Smad2／3蛋白表达（P〈0．01）,使肝细胞变性程度与胶原纤维增生程度显著降低。结论五灵胶囊治疗肝纤维化的作用机制是显著降低肝纤维化大鼠组织肝细胞变性和胶原纤维增生的程度、抑制TGF-β／Smad及Ras／ERK信号通路TJ3RI、Rasp21、p-ERK蛋白表达及TGF-β1过量分泌。     

利拉鲁肽对糖尿病大鼠肾组织局部肾素-血管紧张素系统活性及转化生长因子β1表达的影响

目的：探讨利拉鲁肽是否能够抑制糖尿病大鼠肾组织局部肾素-血管紧张素系统（RAS）,进而下调转化生长因子（TGF）-β1表达。方法给予4周龄雄性Wistar大鼠高糖高脂饲料喂养联合小剂量链脲佐菌素鼠尾静脉注射建立糖尿病大鼠模型20只,采用随机数字表法分为糖尿病组和利拉鲁肽组,每组10只,同时设对照组10只。利拉鲁肽组予以利拉鲁肽（400μg· kg-1· d-1）皮下注射,对照组和糖尿病组大鼠给予等量生理盐水皮下注射。12周后,应用实时定量聚合酶链反应（PCR）、Western blotting法检测比较各组大鼠肾组织血管紧张素Ⅱ1型受体（AT1R）和TGF-β1表达的变化,酶联免疫吸附实验检测各组肾组织血管紧张素（ Ang）Ⅱ的表达,Masson染色观察各组大鼠肾组织胶原沉积情况。采用单因素方差分析比较组间差异,两两比较采用LSD检验。结果 Masson染色显示,糖尿病组大鼠肾组织胶原纤维沉积对照组明显增多,利拉鲁肽组大鼠肾组织胶原纤维沉积较糖尿病组少。糖尿病组大鼠肾组织AngⅡ表达显著高于对照组（t＝3.444,P＜0.05）,利拉鲁肽组大鼠肾组织AngⅡ表达则较糖尿病组显著降低（ t＝2.614,P＜0.05）。糖尿病组大鼠肾组织AT1R、TGF-β1 mRNA和蛋白表达显著高于对照组（t＝4.084、3.714、9.381、6.408,均P＜0.05）。利拉鲁肽组大鼠肾组织AT1R、TGF-β1mRNA和蛋白表达显著低于糖尿病组（ t＝3.487、2.907、5.033、2.295,均P＜0.05）。结论利拉鲁肽可抑制糖尿病大鼠肾组织TGF-β1的表达发挥肾保护作用,可能与其抑制肾组织局部RAS活性有关。     

内皮型一氧化氮合酶在慢性乙型肝炎肝组织中的表达

目的研究内皮型一氧化氮合酶(endothelium-type nitric oxide synthase,eNOS)在慢性乙型肝炎肝组织中的表达及其与病理改变的关系。方法应用免疫组化法观察了41例慢性乙型肝炎患者肝组织中eNOS的变化。结果 eNOS见于肝细胞,窦内皮细胞,枯否细胞,血管内皮细胞,单个核细胞,及增生的卵圆细胞,呈胞浆型,细颗粒型,粗颗粒型及胞膜型分布,以肝细胞为主,在炎症病变活动区相对集中。并发现其表达随肝组织病变活动程度增加而增强,与炎症程度的相关系数为0.5327(P<0.05),与纤维化程度无明显相关性。结论 eNOS与慢性乙肝肝组织病理改变密切相关。     

慢性乙型肝炎患者肝组织病理研究

目的:探讨慢性乙型肝炎(CHB)患者临床表现和病理诊断的相关性.方法:收集30例CHB患者的临床资料,分析临床表现与病理诊断的相关性.结果:肝组织的炎症和纤维化程度的相关性显著(r=0.659,P＜0.01),白蛋白/球蛋白比值(A/G)与肝脏炎症和纤维化分级显著负相关(r=-0.368,P＜0.05;r=-0.401,P＜0.05).年龄、性别及其他化验指标如ALT、AST、TP、ALB、GLO、TBil、PLT、PT、PTA、门静脉宽度、脾脏厚度等与肝组织炎症和纤维化分级无显著相关性(P＞0.05).结论:慢性乙型肝炎肝脏炎症和纤维化的严重程度密切相关,仅根据肝功能判断轻中度的CHB患者的肝脏炎症及纤维化程度有相当的局限性.     

Intrahepatic Expression of C-C Motif ligand 5 in Patients with Chronic Hepatitis B

Background: C-C motif ligand 5 (CCL5) is reported to play a key role in acute and chronic liver diseases. However, the association between CCL5 and chronic hepatitis B (CHB) remains to be explored. We aimed to investigate the CCL5 expression in the liver tissues of CHB patients and compared the CCL5 expression among CHB patients with different stages of liver inflammation and fibrosis. Methods: Liver tissue specimens from 51 CHB patients who underwent liver biopsy and twelve healthy liver donors were included in the present study. CCL5 expression in the liver tissues was analyzed using immunohistochemistry. The hepatic inflammation grades and fibrotic stages of CHB patients were assessed by the Scheuer classification system. Results: Livers of CHB patients exhibited significantly accumulated CCL5+ cells when compared to those of healthy controls (42.80 ± 4.37 vs. 7.25 ± 0.99/HPF, P < .001). CHB patients with higher hepatic inflammation grades had more CCL5+ cells in their livers than those with lower grades (P < .05). However, the numbers of CCL5+ cells were not correlated with the fibrotic stages in CHB patients (r = .073, P = .61). The number of CCL5+ cells in the liver tissues of CHB patients was positively correlated with alanine transaminase levels (r = .278, P = .041) and aspartate aminotransferase levels (r = .328, P = .009). Conclusions: CHB patients have a significant accumulation of CCL5+ cells in the liver, and CCL5 may play a pathological role in hepatic inflammation of CHB.     

慢性乙型肝炎患者肝组织LXRα和CYP7A1基因水平变化及其与肝组织炎症和纤维化程度的关系研究*

目的 探讨慢性乙型肝炎(CHB)患者肝X受体α(LXRα)和细胞色素P450亚型7A1(CYP7A1)基因表达水平与肝组织病理学炎症和纤维化程度的关系。方法 2019年1月～2020年10月我院收治的CHB患者118例,均接受肝穿刺活检,将炎症活动度分级＞G2和肝纤维化分期＞S2定义为肝组织炎症或纤维化程度显著;采用免疫组织化学染色法检测肝组织LXRα和CYP7A1表达,采用RT-PCR法检测LXRα mRNA和CYP7A1 mRNA水平。结果 118例CHB患者肝组织LXRα和CYP7A1蛋白和/或其mRNA阳性分别为78.0%和73.7%;38例肝组织显著炎症组LXRα mRNA和其蛋白(AOD)水平分别为(0.6±0.2)和(0.3±0.1),显著高于80例非显著炎症患者[分别为(0.4±0.1)和(0.1±0.0),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.8±0.2)和(0.4±0.1),显著高于非显著炎症患者[分别为(0.3±0.1)和(0.1±0.0),P<0.05];48例显著肝纤维化组肝组织LXRα mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于70例非显著肝纤维化患者[分别为(0.3±0.1)和(0.1±0.1),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于非显著肝纤维化患者[分别为(0.4±0.2)和(0.2±0.1),P<0.05]。结论 LXRα和CYP7A1表达上调可能参与了CHB患者肝组织炎症和肝纤维化发生发展过程,其机制值得进一步研究。     

Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis

BACKGROUND/AIMS: To study the effects of interleukin-10 on hepatic stellate cells and liver tissue in experimental rats hepatic fibrosis. METHODOLOGY: Rat hepatic fibrosis model induced by carbon tetrachloride was established. Liver tissues were harvested from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. The expression of TGF-beta1, MMP-2 and TIMP-1 in the liver tissues was measured by S-P immunohistochemistry. In addition, another model was established; HSCs in rats in each group were isolated. RT-PCR was employed to analyze TGF-beta1, MMP-2 and TIMP-1 mRNA expression in cells and immunocytochemistry was performed to detect protein expression of alpha-SMA, NF-kappaB, TGF-beta1, MMP-2 and TIMP-1 in HSCs. RESULTS: Rat hepatic fibrosis was developed successfully. The fibrosis changes were partially reversed by simultaneous administration of IL-10. The positive signals of TGF-beta1, MMP-2 and TIMP-1 were observed more frequently (P<0.05) in the CCl4-treated group compared to those in the IL-10-treated group and the control group. HSCs were successfully isolated. TGF-beta1, MMP-2 and TIMP-1 mRNA in HSCs increased obviously during the course of hepatic fibrosis, and their levels were decreased after the treatment with IL-10 (P<0.05). The immunocytochemistry positive levels for TGF-beta1, MMP-2, TIMP-1, alpha-SMA and NF-kappaB in the fibrogenesis group were increased significantly compared to the normal group (P<0.01). The positive signals decreased significantly (P<0.05) after the treatment with IL-10. CONCLUSIONS: The expression of TGF-beta1, MMP-2 and TIMP-1 increased in liver or in HSC of hepatic fibrosis rats and decreased after treatment with IL-10. The IL-10 could inhibit the activation of HSCs and make an antifibrogenic process come into effect in this way.     

Increased expression of Ob-Rb and its relationship with the overexpression of TGF-beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis.

AIMS: The main aim of this study was to examine the relationship of the leptin system in steatosis and nonalcoholic steatohepatitis (NASH). The study also analysed the pathogenic role of the leptin system in the development of hepatic fibrosis and its relation with the TGF-beta1 system. MATERIALS AND METHODS: The study included 90 subjects, 55 with NASH and 35 with simple steatosis. Gene expression of leptin, leptin receptor and TGF-beta mRNA was analysed by real-time PCR on liver tissue. Leptin serum levels were determined by RIA. Leptin receptor expression was also assessed by immunohistochemistry. RESULTS: Increased expression was found for leptin receptor mRNA (P=0.0016) and its protein (P<0.05) in patients with NASH, especially those with fibrosis. There was a marked increase in gene expression of TGF-beta1 in patients with NASH (P=0.0002). A strong correlation was demonstrated between leptin receptor gene expression and TGF-beta1 gene expression (P=0.023). No leptin expression was found in the liver tissue. All patients showed a marked hyperleptinemia, which was closely related to the anthropometric characteristics analysed and independent of development or not of NASH. CONCLUSIONS: The results of the study demonstrate for the first time increased leptin receptor expression in liver tissue and its relationship with overexpression of TGF-beta1 and the degree of hepatic fibrosis.     

熊脱氧胆酸促进肝脏部分切除后肝细胞再生

目的 探讨熊脱氧胆酸（ｕｒｓｏｄｅｏｘｙｃｈｏｌｉｃ ａｃｉｄ，ＵＤＣＡ）对胆道梗阻肝脏部分切除（ＰＨ）后肝细胞再生的影响。方法Ｗｉｓｔａｒ大鼠随机分为正常７０％肝部分切除组（Ｎ－ＰＨ）、胆道梗阻２周７０％ＰＨ组（ＢＤＯ－ＰＨ）、ＢＤＯ—ＰＨ ＵＤＣＡ治疗组及ＢＤＯ—ＰＨ生理盐水治疗组。观察肝组织学改变，检测７０％ＰＨ后肝细胞ＢｒｄＵ标记、肝内肝细胞生长因子（ＨＧＦ）及其受体Ｍｅｔ ｍＲＮＡ表达。结果 ＵＤＣＡ治疗能促进胆道梗阻后肝功能好转并减轻肝组织学病变；ＵＤＣＡ治疗组大鼠７０％ＰＨ后肝内ＨＧＦ／Ｍｅｔ ｍＲＮＡ高峰表达值均高于ＢＤＯ—ＰＨ组（Ｐ ＜ ０．０５），肝细胞 ＢｒｄＵ高峰标记指数（５９．３９±１０．８２）％高于 ＢＤＯ—ＰＨ组肝细胞 ＢｒｄＵ高峰标记指数（３６．２２±８．３７％（ｔ＝４．１４９，Ｐ＜０．０１），而与Ｎ－ＰＮ组肝细胞ＢｒｄＵ高峰标记指数（６８．６４±１１．２６％）％相比差异无显著性（ｔ＝１．４５１，Ｐ＞０．０５）。结论 ＵＤＣＡ通过缓解胆道梗阻后肝组织损害并上调７０％ＰＨ后肝内ＨＧＦ／Ｍｅｔ ｍＲＮＡ表达，从而促进胆道梗阻肝脏部分切除后肝细胞再生。     

Overexpression of p28／gankyrin in human hepatocellular carcinoma and its clinical significance

AIM：To investigate the expression of p28/gankyringene and its role in the carcinogenetic process of human hepatocellular carcinoma(HCC).METHODS:64specimens of HCC and para-carcinoma tissues,22specimens of non-tumor liver tissues(7normal,15cirrhosis),10 specimens of normal human tissues and 5hepatoma cell lines were studied for the expression of p28/gankyrinby Northern blot.The expressionof p28/gankyrin protein was detected immunohistochemically by using the specific polyclonal antibody.RESULTS:Northern blot analysis indicated that the expression of p28/gankyrinmRNA was intensively distributed in brain and heart,weakly in lung,spleen and muscle,undetectable in digestive system including liver,pancreas,stomach,small and large intestines.p28/gankyrinmRNAwas absent in normal liver,weakly detected in liver cirrhosis and in 18of 64para-carcinoma liver tissues.In contrast,the expression of p28/gankyrinmRNA was intensitely detected in all5hepatoma cell lines tested,markedly increased in 57of 64and moderately increased in 5of64HCCsamples.In comparison with liver cirrhosis and para-carcinoma liver tissues.the average expression of p28/gankyrinmRNAin HCCwas increased3.6-(2.901&#177;0.507vs0.805&#177;0.252,P&lt;0.05)and5.2-fold(2.901&#177;0.507vs0.557&#177;0.203,p&lt;0.01),respectively.In addition,p28/gankyrinmRNA expression level was higher in HCCwith portal vein tumor thrombus and microscopic hepatic vein involvement(P=0.021and P=0.047,respectively).Theoverexpression of p28/gankyrin protein in HCCwas targeted in hepatic tumor cells,not in bile duct cells and other interstitial cells.Plays an important role and contributes to the metastasis potential in the process of carcinogenesis.p28/gankyrinmay become a specific biological tissue marker for the pathological diagnosis of HCC.     

Expression of growth hormone receptor and its mRNA in hepatic cirrhosis

AIM: To investigate the expression of growth hormone receptor (GHR) and mRNA of GHR in cirrhotic livers of rats with the intension to find the basis for application of recombinant human growth hormone (rhGH) to patients with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in SpragueDawley rats by administration of thioacetamide intraperitoneally for 9-12 weeks. Collagenase Ⅳ was perfused in situ for isolation of hepatocytes. The expression of GHR and its mRNA in cirrhotic livers was studied with radio-ligand binding assay, RT-PCR and digital image analysis.RESULTS: One class of specific growth hormone-binding site, GHR, was detected in hepatocytes and hepatic tissue of cirrhotic livers. The binding capacity of GHR (RT, fmol/mg protein) in rat cirrhotic liver tissue (30.8±1.9) was significantly lower than that in normal control (74.9±3.9) at the time point of the ninth week after initiation of induction of cirrhosis (n=10, P＜0.05), and it decreased gradually along with the accumulation of collagen in the process of formation and development of liver cirrhosis (P＜0.05). The number of binding sites (×10 4/cell) of GHR on rat cirrhotic hepatocytes (0.86±0.16) was significantly lower than that (1.28±0.24)in control (n= 10, P＜0.05). The binding affinity of GHR among liver tissue, hepatocytes of various groups had no significant difference (P＞0.05). The expression of GHR mRNA (riOD,pixel) in rat cirrhotic hepatic tissues (23.3±3.1) was also significantly lower than that (29.3±3.4) in normal control (n=10, P＜0.05).CONCLUSION: The growth hormone receptor was expressed in a reduced level in liver tissue of cirrhotic rats,and lesser expression of growth hormone receptors was found in a later stage of cirrhosis. The reduced expression of growth hormone receptor was partly due to its decreased expression on cirrhotic hepatocytes and the reduced expression of its mRNA in cirrhotic liver tissue.