枯否氏细胞在大鼠非酒精性脂肪性肝炎发病中的作用

目的：探讨枯否氏细胞大鼠非酒精性脂肪性肝炎（non-alcoholic steatohepatitis,NASH)发病中的作用,方法：19只雄性SD大鼠随机分为模型组（10只）和正常组（9只）,分别预高脂肪饮食和标准饮食饲养12周,HE梁色观察肝细胞切片病理学改变,透射电镜和溶菌酶免疫组织化学染色观察枯否氏细胞的数量和形态。结果：模型组大鼠均出现肥胖,高脂血症伴肝细胞大泡性脂肪变,小叶内炎症细胞浸润和坏死,与正常相比,模型组肝小叶内枯否氏细胞数显著增加,并呈活化状态,模型组枯否氏细胞变化与其肝病理学改变相一致,结论：高脂饮食大鼠肝脏枯否氏细胞增多,并可能与其脂肪性肝炎的发病有关。     

枯否细胞功能状态对实验性急性肝功能衰竭的影响

实验采取先激活或抑制枯否细胞功能，后用硫代乙酰胺引发大鼠的严重肝损伤，以观察不同功能状态枯否细胞在急性肝功能衰竭发生发展中的作用，实验结果表明，激活枯否细胞功能，可使肝损伤与肠源性内毒素血症减轻；抑制枯否细胞功能，肝损伤虽无明显改变，但肠源性内毒素血症加重，同时出现严重肾功能障碍与肝性昏迷，上述结果提示，肠源性内毒素在血症在包性肝功能衰竭发生中具有决定性作用。     

枯否细胞在高脂饮食致小鼠慢性肝损伤发生中的作用

目的探讨枯否细胞（Kupffer cell，KCs）在高脂饮食致小鼠慢性肝损伤发生中的作用。方法小鼠给予高脂饮食复制慢性肝损伤模型，实验动物随机分为对照组和模型组。12周后，小鼠腹主动脉采血测定血浆丙氨酸氨基转移酶（ALT）、内毒素（LPS）水平；肝组织用于组织病理切片的制备及肿瘤坏死因子α（TNF-α）水平检测。分离培养小鼠KCs，测定其吞噬聚苯乙烯乳珠的能力及在LPS刺激下TNF-α的分泌；采用Western blot方法检测KCs CD14的表达。结果模型组小鼠血清ALT、LPS及肝组织TNF-α水平均明显高与对照组（t=2．87～30．11，P〈0．01）。KCs分离培养表明，模型组小鼠KCs呈活化状态，吞噬聚苯乙烯乳珠能力降低（t：5．04，P〈0．01），LPS刺激后TNF-α的分泌明显增加（t=4．17，P〈0．01）。Westernblot结果显示，模型组小鼠KCsCD14受体表达上调。结论在高脂饮食所致小鼠慢性损伤时，虽KCs处于活化状态，但其吞噬功能降低而分泌TNF-α能力则增强。提示KCs功能紊乱与高脂饮食致小鼠慢性肝损伤发生密切相关。     

虎眼万年青对急性肝损伤大鼠肝脏枯否氏细胞的影响

目的探讨虎眼万年青对急性肝损伤大鼠肝脏枯否氏细胞（KC）的影响。方法将实验大鼠随机分为正常对照组、四氯化碳（CCl4）急性肝损伤组、甘草酸二胺防治对照组、虎眼万年青防治组,HE染色观察肝组织病理变化,免疫组织化学法观察肝组织溶菌酶蛋白（MOD）的表达、了解KC的变化。结果虎眼万年青能显著改善肝组织炎性反应,虎眼万年青防治组大鼠肝组织MOD表达较模型组显著降低（P〈0．01）,且优于甘草酸二胺防治对照组（P〈0．01）。结论虎眼万年青能够抑制KC表达,可能是其防治急性肝损伤的作用机理之一。     

枯否细胞在肝纤维化中的作用

枯否细胞(Kupffer cells,KC)是肝脏内一种重要的非实质细胞,其在发挥防御作用的同时,可释放多种化学介质介导肝脏损伤,在诸多肝脏病理性改变中起重要作用.肝纤维化(hepatic fibrosis,HF)是诸多慢性肝病共同的病理过程,也是各种慢性肝病向肝硬化转归的中转站.KC分泌的细胞因子作为重要的影响因素,参与HF的发生与发展.因此,深入研究KC在HF发生与发展中的作用和机制,并研究与KC相关的抗纤维化治疗策略及方法,对于临床工作中防治肝脏损伤,提高患者生存率具有实际意义.     

鲜生地对肝损伤模型大鼠枯否细胞功能的影响

目的探讨鲜生地在大鼠肝损伤时对肝脏枯否细胞功能的影响。方法取健康成年大鼠64只,随机分成4组:假手术组,肝损伤组,肝损伤+鲜生地组和肝损伤+乳果糖组。前两组以生理盐水灌胃,后两组分别以鲜生地和乳果糖灌胃。观察大鼠血浆内毒素(ET)、肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、谷丙转氨酶(ALT)以及枯否细胞表面CD68蛋白表达。结果与肝损伤组比较,鲜生地组和乳果糖组血浆ET、TNF-α、IL-1、ALT明显降低(P<0.05),CD68蛋白表达减少。结论鲜生地具有抑制肝脏枯否细胞吞噬及分泌作用,减少炎症因子释放,从而减轻肝细胞损伤。     

枯否氏细胞,肝细胞对疟原虫子孢子感染和发育的影响

１次接种９００万约氏疟原虫子孢子悬液，３０ｍｉｎ后的肝脏超微结构显示，枯否氏细胞吞噬复合体，邻近肝细胞线粒体空泡化，嵴突消失；枯否氏细胞内可见形态退变的子孢子；线粒体、内质网、核糖体丰富的肝细胞内子孢子结构清晰；线粒体空泡化、嵴突消失的肝细胞内子孢子退变；子孢子进入枯否氏细胞或肝细胞的时间不玫，１个肝细胞内可见２个子孢子。     

枯否细胞与肝纤维化

肝纤维化时枯否细胞可分泌多种细胞因子及胶原酶等生物活性物质，并由此对肝细胞外基质的合成与降解起调控作用，在肝纤维化的发生发展中起着重要作用。     

枯否细胞活化在非酒精性脂肪性肝病发生和发展中的作用

枯否细胞(kupffer ceils,KCs)是体内最大的一类固有巨噬细胞群,其解剖学位置有利于行使特定的生物学功能.KCs能够快速识别外源性和内源性的潜在危险信号并活化,在危险识别、免疫耐受、脂质平衡和非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)进展中发挥重要作用.     

库普弗细胞与肝纤维化的关系

活化的库普弗细胞发挥吞噬、抗原提呈、释放细胞因子、免疫调节等功能，成为机体防御的重要屏障，同时也参与了肝脏的炎症损伤、纤维化的形成和降解等病理过程。     

Role of Kupffer cells in the pathogenesis of liver disease

INTRODUCTION The sinusoidal lining of the liver contains the nonparen-chymal cell populations which consist of Kupffer cells (KCs), sinusoidal endothelial cells (SEC) and stellate cells (SC). All three cell-types seem to play a crucial role in liver homeo…     

雷抑素对大鼠移植肝Kupffer细胞的影响

目的探讨肝移植术前应用雷抑素对大鼠肝Ｋｕｐｆｅｒ细胞的影响方法以ＳＤ大鼠为供受体建立原位肝移植模型．受体移植术前３ｄ连续口服１％羧甲基纤维素１ｍｌ／ｄ（对照组）或雷抑素１０ｍｇ／ｋｇ·ｄ（用药组）．分别于术后１，２，３，２４ｈ采血并取肝组织，检测血清ＴＮＦ，ＡＬＴ及肝ＭＤＡ水平，观察肝超微结构及大鼠１周存活率变化．结果对照组移植术后３ｈ血清ＴＮＦ（５３ｋＵ／Ｌ±０４１ｋＵ／Ｌ），肝ＭＤＡ（４８４６ｎｍｏｌ／ｇ±２３６ｎｍｏｌ／ｇ）显著增加，ＴＮＦ表达呈强阳性；而且药组ＴＮＦ（０９ｋＵ／Ｌ±０１１ｋＵ／Ｌ）肝ＭＤＡ（３６１８ｎｍｏｌ／ｇ±１５４ｎｍｏｌ／ｇ）无明显变化，ＴＮＦ表达阴性，两者相差显著Ｐ＜００１）．电镜检查，对照组肝Ｋｕｐｆｅｒ细胞呈活化表现，而用药组肝Ｋｕｐｆｅｒ细胞呈非活化状态．对照及用药组术后１周存活率分别为０％和６０％．结论术前应用雷抑素可抑制移植肝ＴＮＦ和Ｏ２的产生，抑制Ｋｕｐｆｆｅｒ细胞活化，以减轻肝冷缺血再灌注损伤．     

一种简易分离大鼠肝脏库普弗细胞的方法

目的建立一种经济、简单、稳定的大鼠肝脏库普弗细胞(KCs)分离方法。方法采用前灌流液(D-Hanks)和胰酶消化液两步法原位灌注大鼠肝脏,低速离心去除肝细胞,Percoll分离液不连续密度梯度离心法和选择性贴壁法纯化KCs,将培养7 d的KCs采用吞噬latex-beads实验及ED1免疫细胞化学法鉴定并检测其纯度。结果每只大鼠肝脏KCs的得率为(1.2～1.8)×107个,细胞存活率达95%,KCs纯度近100%。结论此新方法分离获得的KCs细胞得率和纯度较高且较稳定,同时较传统方法胶原酶的使用相比,此方法更经济实用。     

Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells

AIM: To observe the effects of augmenter of liver regeneration (ALR) on Kupffer cells and to determine whether ALR promotes hepatocyte proliferation induced by Kupffer cells. METHODS: Kupffer cells and hepatocytes were cultured in vitro and various concentrations of recombinant rat ALR (rrALR) were added. 3H-thymidine, BrdU and 3H-leucine incorporation was determined in cultured Kupffer cells and hepatocytes, in hepatocytes conditioned by Kupffer cells, and in associated medium. rrALR was labeled by iodination and used to determine its binding activity by Scatchard analysis in Kupffer cells and primarily cultured rat hepatocytes. RESULTS: rrALR stimulated DMA replication in Kupffer cells and protein synthesis both in cells and in medium in a non-concentration-dependent manner. The effect was significant at the concentration of 1μg/L ALR. However, rrALR had no effect on primarily cultured hepatocytes, when hepatocytes were cultured with the Kupffer cell medium conditioned by ALR, DNA replication and protein synthesis in hepatocytes increased significantly at the concentration of 1μg/L ALR. When the ALR concentration was increased, its effect on hepatocyte proliferation decreased to the basal level. Scatchard analysis indicated the presence of a single class of high affinity receptors with a dissociation constant (Kd) of 0.883 nmol/L and a maximum binding capacity (Bmax) of 126.1 pmol/g protein in the rat Kupffer cells. CONCLUSION: ALR can promote hepatocyte proliferation induced by Kupffer cells, which is associated with the concentration of ALR, suggesting that Kupffer cells play a dual role in liver regeneration.     

Chlamydia pneumoniae replicates in Kupffer cells in mouse model of liver infection

INTRODUCTIONChlamydia pneumoniae(C.pneumoniae)is a common cause of respiratory infections in humans[1,2],and it is also associated with outcomes other than respiratory disease,including coronary heart disease and myocardial infarction[3,4].Systemic diseas…     

Isolation of Kupffer cells and their suppressive effects on T lymphocyte growth in rat orthotopic liver transplantation

AIM: To develop a practical method for isolation, purifi cation and culture of hepatic Kupffer cells (KCs) and to observe their suppressive effects on the proliferation of alloreactive T cells. METHODS: Perfusion in situ in vivo combined with density gradient centrifugation was applied in isolation, purifi cation and culture of hepatic KC. The suppression by KCs on the T cell proliferation in mixed lymphocyte reaction (MLR) was observed. RESULTS: This method resulted in a satisfactorily high yield of (1.1 ± 0.2) × 107 KCs per liver, (93.5/ ± 1.8/) viable cells, over 90/ purity and positive for ED-2. After the first 24 h in culture, a great number of KCs which exhibited typical characteristics were observed. Using 3H-TdR incorporation assay, non-irradiated KCs significantly suppressed allo-MLR. The KCs recovered from accepted liver allografts in groups D and E were more effective in suppressing allo-MLR. CONCLUSION: A standardized procedure for isolation of highly purified rat KCs is proposed and KCs have suppressive effects on the proliferation of alloreactive T cells, especially those derived from accepted liver allografts.     

Expression of macrophage inflammatory protein-1α in Kupffer cells following liver ischemia or reperfusion injury in rats

AIM: To explore the expression of macrophage inflammatory protein-1α (MIP-1α) in Kupffer cells (KCs)following liver ischemia/reperfusion injury IRI in rats.METHODS: Forty male SD rats were divided randomly into five groups. A model of partial warm ischemia/reperfusion injury in the rat liver was established. KCs were isolated and incubated one hour, six hours, 12 h,and 24 h after the reperfusion. Tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) in the supernatants were measured by ELISA. MIP-1α in KCs was detected by immunocytochemical and RT-PCR.RESULTS: No or few MIP-1α protein and mRNA were expressed in the KCs of the control group. Its expression in the IRI group had a significant increase after the reperfusion (P ＜ 0.05), which was contrary to the control group.CONCLUSION: The active behavior of the MIP-1α gene in KCs following liver ischemia/reperfusion injury is assumed to be one of the major causes for the hepatic ischemia/reperfusion injury.     

库普弗细胞在酒精性肝病发病机理中的作用

库普弗细胞(KC)是肝内定居的巨噬细胞,由于其细胞表面存在多种受体,可被多种配体和激活剂激活,通过产生反应氧、细胞因子和炎症介质等贯穿于酒精性肝病的发病过程,控制KC的活化将有助于减轻或阻止酒精性肝病的肝脏病变。