Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

血红素氧合酶-1与脑出血的继发性损害

自发性脑出血是指非外伤性脑实质出血,发病率高,死亡率高[1],且脑出血后患者多遗留不同程度的神经功能障碍。因此,探讨脑出血后脑组织损伤的病理生理机制对于改善脑出血病情及预后是十分必要的。大量研究表明自发性脑出血后造成的脑损伤存在多种机制[2]:早期血肿机械占位效应、     

重组血红素加氧酶-2在大肠杆菌中表达与纯化方法的研究

目的　确定重组血红素加氧酶 2在大肠杆菌中表达与纯化方法。方法　将已构建的血红素加氧酶 2(HO 2 )的重组质粒pMW1 72a HO 2转入大肠杆菌BL 2 1 ,分析不同温度及摇床转速对HO 2表达的影响 ,确定可溶性表达最佳条件。使用超声波、超速离心、分级盐析、分子筛层析等方法纯化HO 2。检测酶活性。结果　确定了HO 2可溶性表达最佳条件为 37℃ ,(85± 5 )r min ;确定了HO 2具体纯化路线。得到蛋白纯度为 95 .0 % ,纯化倍数为 2 .9倍 ,收得率为 4 0 .9%的活性HO 2蛋白。结论　获得了纯度高、具有活性的HO 2蛋白 ,为进一步进行HO 2结构与功能之间关系的研究提供了可行的纯化路线     

红细胞对创伤性脑内出血大鼠脑含水量及HO-1表达的影响

目的研究大鼠创伤性脑内出血(TICH)中红细胞对脑含水量和血红素氧合酶-1(HO-1)表达的影响,并分析二者的关系,以探讨红细胞在TICH后脑水肿形成中的作用机制。方法120只大鼠随机分为创伤性脑损伤组(TBI组),TBI加注全血组(WB组),TBI加注溶解红细胞组(LRBC组)和TBI加注压积红细胞组(PRBC组),每组30只。4组均采用自由落体打击法造成大鼠脑外伤。后3组借助立体定向仪分别向伤区脑皮质内注射全血、溶解红细胞或压积红细胞,造成TICH模型。每组于伤后1、3、5d分别处死10只大鼠,5只测伤区脑组织含水量,5只用免疫组化法检测HO-1的表达。结果4组组内比较:TBI、WB和PRBC3组第3d的脑含水量最高(分别为82.85%±0.60%,85.00%±1.12%,84.93%±1.21%),LRBC组第1d的含水量最高(84.44%±0.85%;4组间比较,1d时LRBC组含水量最高,3d时WB和PRBC组含水量最高。在WB、PRBC和LRBC组,HO-1阳性表达的强弱与脑含水量的高低变化相一致。结论红细胞在TICH后迟发性脑水肿的形成中有重要作用,其机制涉及红细胞的降解产物。     

右美托咪定调控Nrf2/HO-1通路对H2O2诱导心肌细胞氧化应激损伤的作用研究

目的 探讨右美托咪定调控核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)通路对过氧化氢(H₂O₂)诱导心肌细胞氧化应激损伤的作用。方法 体外培养大鼠H9C2心肌细胞,设置对照组、H₂O₂组、1μmol右美托咪定+H₂O₂组、5μmol右美托咪定+H₂O₂组、10μmol右美托咪定+H₂O₂组。CCK-8法检测各组H9C2细胞增殖情况;酶联免疫吸附试验(ELISA)检测各组H9C2细胞丙二醛(MDA)、超氧化物歧化酶(SOD)水平;实时荧光定量聚合酶链反应(q RT-PCR)检测各组H9C2细胞Nrf2、HO-1 mRNA相对表达量;Western blotting检测各组H9C2细胞Nrf2、HO-1蛋白相对表达量。结果 与对照组比较,H₂O₂组H9C2细胞存活率、SOD水平、Nrf2、HO-1 mRNA及蛋白相对...     

血红素加氧酶1延长异种心脏移植存活的机制研究

探讨血红素加氧酶1(heme oxygenase-1,HO-1)在器官移植中抗急性血管排斥反应的作用。通过建立豚鼠到SD大鼠异位心脏移植模型,用血红素(hemin)分别诱导供者和受者,上调HO-1基因表达;用眼镜蛇毒因子、环孢素A抑制超急性排斥反应;观测供者心脏存活时间,并分别检测心脏组织HO-1表达、受者血清异种抗体IgM的变化及异种抗体IgM和C3在血管内膜的沉积;采用TUNEL方法检测心脏组织细胞凋亡;RT-PCR方法测定组织CD40L mRNA表达水平。结果显示:上调HO-1表达能明显延长心脏移植存活时间,抑制异种抗体IgM表达和在血管内膜的沉积,减少心肌细胞的凋亡并且抑制CD40L mRNA的表达。该结论表明HO-1通过介导CD40-CD40L共刺激途径抑制大鼠异种心脏移植后急性血管排斥反应,延长心脏移植存活时间。     

RDP1258对大鼠脾细胞增殖及HO-1活性的抑制作用

目的 :观察一种新型HLA衍生肽 (RDP12 5 8)的免疫抑制作用 ,并探讨其机制。方法 :用化学方法合成一种HLA衍生肽(RDP12 5 8) ,以3 H TdR掺入法观察其在体外对大鼠脾细胞增殖的影响 ;以酶化学法观察其对脾细胞血红素氧合酶 1(hemeoxygenase 1,HO 1)活性的影响。结果 :RDP12 5 8可显著抑制大鼠脾细胞增殖并以剂量依赖的方式降低HO 1的活性。结论 :RDP12 5 8能够显著抑制丝裂原或同种抗原刺激所致大鼠脾细胞的增殖反应 ,其抑制作用可能是通过降低HO 1活性而实现的     

Heme oxygenases in pregnancy II: HO-2 is downregulated in human pathologic pregnancies

PROBLEM: We previously reported a diminished expression of the heme-degrading enzymes heme oxygenases (HO)-1 and HO-2 in decidua and placenta from mice undergoing Th1-mediated abortion, strongly indicating the protective effect of HO in murine pregnancy maintenance. Here we investigated whether the expression of HO-1 and HO-2 is also reduced at the feto-maternal interface of pathologic human pregnancies. METHOD OF STUDY: Immunohistochemistry was used to detect HOs expression in placental and decidual first-trimester tissue from patients with: spontaneous abortion (n = 14), choriocarcinoma (n = 14), hydatidiform mole (H-mole) (n = 12), compared with normally progressing pregnancies (n = 15). Further, we investigated early third-trimester decidual and placental tissue from patients with pre-eclampsia (n = 13) compared with fetal growth retardation (n = 14) as age-matched controls. RESULTS: In first trimester tissue, we observed a significant reduction of HO-2 expression in invasive trophoblast cells, endothelial cells, and syncytiotrophoblasts in samples from patients with spontaneous abortion compared with normal pregnancy. H-mole samples showed a diminished expression of HO-2 in invasive trophoblast cells and endothelial cells in comparison with NP, whereas choriocarcinoma samples showed no significant differences compared with the control. In third trimester tissue, HO-2 was also reduced in syncytiotrophoblasts and invasive trophoblast cells from pre-eclampsia compared with samples from fetal growth retardation. HO-1 expression was diminished in all pathologies investigated; however, the differences did not reach levels of significance. CONCLUSIONS: Our data indicate that HOs play a crucial role in pregnancy and low expression of HO-2, as observed in pathologic pregnancies, may lead to enhanced levels of free heme at the feto-maternal interface, with subsequent upregulation of adhesion molecules, allowing enhanced inflammatory cells migration to the feto-maternal interface.