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1.
本工作采用无血清原代培养大鼠肝细胞法,观察了重组人肝细胞生长因子(r-hHGF)对四氯化碳(CCl4)致大鼠肝细胞损伤的保护作用。结果表明,r-hHGF对CCl4染毒肝细胞有明显的保护作用。r-hHGF保护组较CCl4染毒组细胞存活率显著升高,细胞内丙氨酸转氨酶、钾离子漏出明显降低。结果提示,r-hHGF可减轻CCl4对肝细胞膜的损伤,提高细胞膜的结构完整性  相似文献   

2.
重组人肝细胞生长因子抗四氯化碳染毒小鼠肝的保护效应   总被引:5,自引:0,他引:5  
为检测重组人肝细胞生长因子(r-hHGF)的保肝作用,本工作观察到r-hHGF降低CCl4染毒小鼠血清ALT和AST升高的幅度,减轻肝组织受损的程度和防止肝细胞器的破坏,而且,r-hHGF的这种保肝效应所需剂量极小,为ng级。根据上述资料推测,r-hHGF为一极有效的保护小鼠肝抗CCl4损伤的生长因子  相似文献   

3.
利用无血清原代培养大鼠肝细胞,观察重组人肝细胞生长因子(rhHGF)对CCl4染毒肝细胞的保护作用。结果表明:(1)rhHGF(5ng/ml)预自理后可显著提高CCl4(15mmol/L)染毒肝细胞存活率,降低细胞内丙氨酸氨基转移酶(ALT)、K^+的漏出;(2)表皮生长因子(EGF,50ng/ml)和rhHGF(5ng/ml)合用预处理肝细胞,CCl4染毒后细胞内ALT、K^+漏出较rhHGF和  相似文献   

4.
本工作采用3HTdR掺入DNA法观察重组人肝细胞生长因子(rhHGF)刺激大鼠离体肝细胞DNA合成的剂量与时间效应。实验结果表明:rhHGF是最强的促肝细胞分裂剂,在一定剂量范围内,rhHGF与肝细胞DNA合成有明显的量效关系。1ng/mlrhHGF即可引起3HTdR掺入显著增加(P<0.01),随剂量增加,刺激DNA合成的效应也随之增强;10ng/ml时3HTdR掺入量最大,较对照组高7倍(P<0.001),剂量再增加即出现抑制效应;rhHGF刺激肝细胞DNA合成存在时间效应关系,表现为rhHGF作用24h,DNA合成量明显高于对照组(P<0.01),48h作用达最高(P<0.001),随后开始下降,至96h下降到相当于24h的水平。  相似文献   

5.
人肝刺激因子对大鼠实验性慢性肝损伤的保护作用   总被引:3,自引:0,他引:3  
从健康孕妇水囊引产4─6个月龄的胎儿取肝,采用LaBrecque方法提取人肝刺激因子(hHSS)。经3H-胸腺嘧啶核苷参入肝DNA法测定其生物活性。表明此hHSS可刺激肝细胞DNA合成。采用皮下注射CCl4和饮用10%乙醇来制备慢性肝损伤动物模型,观察了hHSS的保护肝脏作用。结果表明:hHSS可使CCl4-乙醇所致慢性肝损伤大鼠的死亡率、血清谷丙转氨酶水平、肝组织中羟脯氨酸含量的升高以及肝组织中丙二醛的含量降低。肝组织切片表明:hHSS能减轻肝组织的损伤程度,促进肝细胞再生,并能明显防止肝纤维化的形成和发展。可见,hHSS对CCl4-乙醇所致的慢性肝损伤大鼠有明显的保护作用,其机制可能与促进肝细胞再生及抑制肝细胞膜的脂质过氧化有关。  相似文献   

6.
采用大鼠离体肝细胞原代培养24h,并利用四氯化碳CCl4造成急性肝细胞损伤模型,检定15-甲基-前列腺素F2α(15-Mt-PGF2α)对肝细胞损伤的影响。结果表明:(1)15-Mt-PGF2α可显著降低中毒肝细胞脂质过氧化物水平,抑制肝细胞脂质过氧化,并降低谷丙转氨酶(GPT)和谷草转氨酶(GOT)水平,稳定脂质膜。(2)显著促进中毒肝细胞RNA和DNA的合成。(3)超微结构证实15-Mt-PGF2α能减轻CCl4对肝细胞脂质膜,染色质,线粒体,内质网和核蛋白体的损害。  相似文献   

7.
用四氯化碳(CCl4)损伤正常大鼠后,采用Western印迹法和免疫组化法观察肝细胞原癌基因(c-fos/c-jun)的表达。Western印迹法表明,当成年大鼠的静息期肝细胞受到CCl4损伤性刺激后,c-fos/c-jun产物(Fos和Jun)水平升高,在CCl4处理后30min开始升高,在4h时消失。8h后Fos/Jun再度出现,并持续24h以上。ICC法表明,Jun阳性细胞为靠近肝中央静脉区  相似文献   

8.
用四氯化碳(CCl4)损伤正常大鼠后,采用Western印迹法和免疫组化法观察肝细胞原癌基因(c-fos/c-jun)的表达。Western印迹法表明,当成年大鼠的静息期肝细胞受到CCl4损伤性刺激后,c-fos/c-jun产物(Fos和Jun)水平升高,在CCl4处理后30min开始升高,在4h时消失。8h后Fos/Jun再度出现,并持续24h以上。ICC法表明,Jun阳性细胞为靠近肝中央静脉区的肝实质细胞。根据上述资料推测,肝受CCl4损伤后肝细胞的原癌基因c-fos/c-jun出现即时的与滞后的两次表达,这与肝细胞进入细胞周期有关,这种基因表达也许可作为肝再生过程中识别特殊体液因子的标志。  相似文献   

9.
利用无血清原代培养大鼠肝细胞,观察重组人肝细胞生长因子(rhHGF)对CCl4染毒肝细胞的保护作用. 结果表明: (1) rhHGF (5 ng/ml)预处理后可显著提高CCl4 (15 mmol/L)染毒肝细胞存活率,降低细胞内丙氨酸氨基转移酶(ALT)、 K+的漏出;(2) 表皮生长因子(EGF,50ng/ml)和rhHGF (5 ng/ml)合用预处理肝细胞,CCl4染毒后细胞内ALT、 K+漏出较rhHGF和EGF单独保护组进一步降低;(3)大鼠肝部分切除和CCl4 (50%,2.5 ml/kg bw)染毒后,再生肝内HGF基因及其受体基因/c-met的表达分别较假手术和盐水对照组显著升高. 结果提示,rhHGF对CCl4染毒大鼠肝细胞具有保护作用;EGF和rhHGF有协同保护作用;HGF及其受体的表达在肝脏再生及修复中可能有重要作用.  相似文献   

10.
血源性和胞源性肝细胞生长因子对肝再生的调控   总被引:1,自引:0,他引:1  
肝再生过程中,血源性肝细胞生长因子(HGF-h)和胞源性肝细胞生长因子(HGF-c)起重要的调控作用。本文通过分析二者与肝再生时相、细胞周期调控基因表达之间的关系,认为它们对肝再生的调控具有时序性。HGF-h作为早期信号,启动肝细胞分裂;而HGF-c仅作用于感受态细胞,促进其分裂。本文还从促再生作用的器官特异性,重症肝炎的临床治疗以及二者的来源等方面对这一推测加以佐证。  相似文献   

11.
A protective effect of Rho-kinase inhibitor on various organ injuries is gaining attention. Regarding liver injury, Rho-kinase inhibitor is reported to prevent carbon tetrachloride (CCl4)- or dimethylnitrosamine-induced liver fibrosis and hepatic ischemia-reperfusion injury in rats. Because Rho-kinase inhibitor not only improved liver fibrosis but also reduced serum alanine aminotransferase (ALT) level in CCl4-induced liver fibrosis, we wondered whether Rho-kinase inhibitor might exert a direct hepatocyte-protective effect. We examined this possibility in acute CCl4 intoxication in rats. Rho-kinase inhibitor, HA-1077, reduced serum alanine ALT level in rats with acute liver injury induced by CCl4 with the improvement of histological damage and the reduction of the number of apoptotic cells. In cultured rat hepatocytes in serum-free condition, HA-1077 reduced apoptosis evaluated by quantitative determination of cytoplasmic histone-associated DNA oligonucleosome fragments with the reduction of caspase-3 activity and the enhancement of Bcl-2 expression. HA-1077 stimulated phosphorylation of Akt, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, abrogated the reduction of hepatocyte apoptosis by HA-1077 in vitro. Furthermore, wortmannin abrogated the reduction of serum ALT level by HA-1077 in rats with acute liver injury induced by CCl4, suggesting that the activation of PI3-kinase/Akt pathway may be involved in the hepatocyte-protective effect by Rho-kinase inhibitor in vivo. In conclusion, Rho-kinase inhibitor prevented hepatocyte damage in acute liver injury induced by CCl4 in rats and merits consideration as a hepatocyte-protective agent in liver injury, considering its direct antiapoptotic effect on hepatocytes in vitro.  相似文献   

12.
A significant increase of the intracellular level of free arachidonic acid was observed in intact rat hepatocytes after poisoning with very low concentrations of CCl4 (0.129-0.172 mM), shown not to exert direct solvent effect. It seems likely that activation of phospholipase A2 (PLA2) is the mechanism mainly responsible for the rise of cytosolic arachidonate, since the latter is prevented by the PLA2 inhibitors indomethacin and mepacrine. The CCl4-induced delay of arachidonic acid incorporation within the cell membrane phospholipids partly contributes to its intracellular accumulation in the early phases of the poisoning. The lack of any significant protection by metabolic inhibitors (SKF 525A, metyrapone), antioxidant compounds (promethazine, diphenylphenylenediamine DPPD) or antioxidant procedures (rat pretreatment with vitamin E) leads to exclude an involvement of CCl4 biotransformation in the increase of intracellular free arachidonate. Finally, the PLA2 inhibitors employed in this study did not afford protection against the enzymic leakage of CCl4-treated hepatocytes.  相似文献   

13.
This study focused on the hepatoprotective activity of C-phycocyanin (C-PC) against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo. In in vitro study, human hepatocyte cell line L02 was used. C-PC showed its capability to reverse CCl4-induced L02 cells viability loss, alanine transaminase (ALT) leakage and morphological changes. C-PC also showed the following positive effects: prevent the CCl4-induced overproduction of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA); prevent changes in superoxide dismutase (SOD) activity; and reduce glutathione (GSH) level. In vivo, C-PC showed its capability to decrease serum ALT and aspartate transaminase (AST) levels in CCl4-induced liver damage in mice. The histological observations supported the results obtained from serum enzymes assays. C-PC also showed the following effects in mice liver: prevent the CCl4-induced MDA formation and GSH depletion; prevent SOD and glutathione peroxidase (GSH-Px) activity; and prevent the elevation of transforming growth factor-beta1 (TGF-β1) and hepatocyte growth factor (HGF) mRNAs. Both the in vitro and in vivo results suggested that C-PC was useful in protecting against CCl4-induced hepatocyte damage. One of the mechanisms is believed to be through C-PCs scavenging ability to protect the hepatocytes from free radicals damage induced by CCl4. In addition, C-PC may be able to block inflammatory infiltration through its anti-inflammatory activities by inhibiting TGF-β1 and HGF expression.  相似文献   

14.
The present study aims to evaluate the hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract on the carbon tetrachloride (CCl(4))-induced hepatocyte damage in fish and provide evidence as to whether it can be potentially used as a medicine for liver diseases in aquaculture. H. sabdariffa extract (100, 200, and 400?μg/mL) was added to the carp primary hepatocyte culture before (pre-treatment), after (post-treatment), and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4) at 8?mM in the culture medium produced significantly elevated levels of lactate dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA) and significantly reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment and pre- and post-treatment of the hepatocytes with H. sabdariffa extract significantly reduced the elevated levels of LDH, GOT, GPT, and MDA and increased the reduced activities of SOD and GSH-Px in a dose-dependent manner; post-treatment did not show any protective effect. The results suggest that H. sabdariffa extract can be potentially used for preventing rather than curing liver diseases in fish.  相似文献   

15.
Previous studies have demonstrated that mice disrupted with the cyclooxygenase-2 gene showed much more severe liver damage compared with wild-type mice after liver injury, and prostaglandins (PGs) such as PGE(1/2) and PGI(2) have decreased hepatic injury, but the mechanisms by which prostaglandins exhibit protective action on the liver have yet to be addressed. In the present study, we investigated the mechanism of the protective action of PGI(2) using the synthetic IP receptor agonist ONO-1301. In primary cultures of hepatocytes and nonparenchymal liver cells, ONO-1301 did not show protective action directly on hepatocytes, whereas it stimulated expression of hepatocyte growth factor (HGF) in nonparenchymal liver cells. In mice, peroral administration of ONO-1301 increased hepatic gene expression and protein levels of HGF. Injections of CCl4 induced acute liver injury in mice, but the onset of acute liver injury was strongly suppressed by administration of ONO-1301. The increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by CCl4 were suppressed by 10 mg/kg ONO-1301 to 39.4 and 33.6%, respectively. When neutralizing antibody against HGF was administered with ONO-1301 and CCl4, the decreases by ONO-1301 in serum ALT and AST, apoptotic liver cells, and expansion of necrotic areas in liver tissue were strongly reversed by neutralization of endogenous HGF. These results indicate that ONO-1301 increases expression of HGF and that hepatoprotective action of ONO-1301 in CCl4-induced liver injury may be attributable to its activity to induce expression of HGF, at least in part. The potential for involvement of HGF-Met-mediated signaling in the hepatotrophic action of endogenous prostaglandins generated by injury-dependent cyclooxygenase-2 induction is considerable.  相似文献   

16.
邵青  梅懋华 《生理学报》1993,45(4):387-394
本工作从自愿流产孕妇的胎儿取肝,按照LaBrecque法提取人肝刺激因子(human hepaticstimulator substance,hHSS)。用荧光探针Fura-2/AM测定离体肝细胞内游离钙,用离子分析仪测细胞染毒(四氯化碳CCl_4)前后基质中钾离子含量,观察hHSS对染毒肝细胞内Ca~(2+)和K~+稳态的影响,并测定肝细胞存活率和细胞内转氨酶(ALT)的漏出作为佐证。结果表明,人胎肝中含有hHSS,hHSS能提高离体肝细胞的存活率,维持肝细胞内游离钙的相对恒定,减少细胞内钾离子和ALT的漏出。这些结果提示,hHSS可保护肝细胞内钙,钾离子稳态和肝细胞膜的稳定,从而加强大鼠离体肝细胞抗CCl_4的损伤。  相似文献   

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