Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO). METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissue malondialdehyde (MDA) content, and severity of hepatic I/R injury. RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs45.3μ10.1 μmol/L, P<0.01). Although serum NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P<0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18μg/L and 0.86±0.11 μmol/g, respectively, P<0.01). I/R induced significant injury to the liver both in M and F groups (P<0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P<0.05 and P<0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P<0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β-estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P<0.01). The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOS-derived NO.     

小凹蛋白与内皮型一氧化氮合成酶在大鼠肝硬化组织中的表达

目的探讨小凹蛋白Caveolin-1、内皮型一氧化氮合成酶eNOS在大鼠肝硬化组织中的异常表达及其意义。方法构建二甲基亚硝胺（DMN）致肝纤维化大鼠模型，在造模4周后观察肝纤维化程度。免疫组织化学染色检测30例大鼠肝硬化肝组织和30例正常大鼠肝组织中Caveolin-1和eNOS的细胞定位；Western Blot检测Caveolin-1和eNOS的蛋白表达水平变化。结果Caveolin-1和eNOS均主要分布于肝窦内皮细胞中，Caveolin-1在肝硬化组表达阳性率为90％，对照组为37％，两组比较差异有统计学意义（P〈0．05）；eNOS在肝硬化组表达阳性率为30％，对照组为66％，两组比较差异有统计学意义（P〈0．05）。Westem Blot检测Caveolin-1在肝硬化组织中较正常肝组织中表达明显增强；eNOS在肝硬化组织中呈低水平表达，较正常肝组织中表达明显减少。结论肝硬化肝窦内皮细胞中Caveolin-1的异常表达促进eNOS-Caveolin-1复合物的生成，结合形式的eNOS活性降低，导致NO合成减少，肝内血管阻力持续增加，从而导致了门静脉高压症的形成。     

The impact of estrogen and L-arginine on serum NO and eNOS expression in aorta of aged rats

Background Cardiovascular diseases (CVD) are less prevalent in postmenopausal women received estrogen replacement therapy (ERT) than those who did not receive ERT.Previous study has shown that the increase of nitric oxide (NO) synthesis is one of the cardioprotective effects of estrogen.This study investigated the effects of estrogen and L-arginine (L-Arg) on serum NO concentrations and the possible regulatory role in endothelial nitric oxide synthase (eNOS) expression in aortas of aged rats.Methods Fifty aged female wistar rats (18-20 months) were randomly divided into five groups (n=10):Sham group (sham operated,0.9 % NaCl 10 μg every three day for 4 months),OVX group (ovariectomized,0.9 % NaCl 10 μg i.m every three day for 4 months),OVE group (ovariectomized + 17β-estradiol 10 μg i.m every three day for 4 months),OVE + L-Arg group (ovariectomized + 17β-estradiol 10ug i.m every three day + 2.25 % L-Arg contained in drinking water every day for 4 months) and L-Arg group (ovariectomized + 2.25 % L-Arg contained in drinking water every day for 4 months).NO concentration and the expression of eNOS mRNA in aorta were measured after 4 months.Results Serum NO synthesis did not alter after ovariectomized (P=0.362),but were increased in OVE group,L-Arg group and OVE + L-Arg group compared with OVX group (P < 0.05,P < 0.05,P < 0.01,respectively).NO concentration also increased in OVE + L-Arg group when compared with OVE group (P < 0.05) or L-Arg group (P < 0.05).There was no significant difference in eNOS mRNA expression in aortas of aged rats between sham,OVX,OVE,OVE + L-Arg and L-Arg group (F=0.550,P=0.700).Conclusions Estrogen treatment and L-Arg supplementation increase serum NO synthesis,but do not upregulate eNOS mRNA expression in aortas of aged rats.     

Effects of ozone oxidative preconditioning on nitric oxide generation and cellular redox balance in a rat model of hepatic ischaemia-reperfusion.

BACKGROUND: Many studies indicate that oxygen free-radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species and protecting against liver ischaemia-reperfusion (I/R) injury. AIMS: In the present study, the effects of ozone oxidative preconditioning (OzoneOP) on nitric oxide (NO) generation and the cellular redox balance have been studied. Methods: Six groups of rats were classified as follows: (1). sham-operated; (2). sham-operated+l-NAME (N(omega)-nitro-l-arginine methyl ester); (3). I/R (ischaemia 90 min-reperfusion 90 min); (4). OzoneOP+I/R; (5). OzoneOP+l-NAME+I/R; and (6). l-NAME+I/R. The following parameters were measured: plasma transaminases (aspartate aminotransferase, alanine aminotransferase) as an index of hepatocellular injury; in homogenates of hepatic tissue: nitrate/nitrite as an index of NO production; superoxide dismutase (SOD), catalase (CAT) and glutathione levels as markers of endogenous antioxidant system; and finally malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) and total hydroperoxides (TH) as indicators of oxidative stress. Results: A correspondence between liver damage and the increase of NO, CAT, TH, glutathione and MDA+4-HDA concentrations were observed just as a decrease of SOD activity. OzoneOP prevented and attenuated hepatic damage in I/R and OzoneOP+l-NAME+I/R, respectively, in close relation with the above-mentioned parameters. CONCLUSIONS: These results show that OzoneOP protected against liver I/R injury through mechanisms that promote a regulation of endogenous NO concentrations and maintenance of cellular redox balance. Ozone treatment may have important clinical implications, particularly in view of the increasing hepatic transplantation programs.     

Inhibition of Inducible Nitric Oxide Synthase Prevents Hepatic, but Not Pulmonary, Injury Following Ischemia-Reperfusion of Rat Liver

The aim of this study was to investigate the contribution of inducible nitric oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO-1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6, 12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of reperfusion in the liver and lung. Plasma nitric oxide levels were increased fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at 12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological examination revealed extensive liver damage, whereas this was not seen in the ONO-1714 group. Lung injury was not significantly changed in groups with versus without ONO-1714. Nitrotyrosine expression was seen in regions similar to those of the histological injuries of the liver, while this staining was absent in the ONO-1714 group. These data show that generation of peroxynitrite could be involved in the pathogenesis of liver injury but not lung injury after hepatic I/R. Inhibition of iNOS could be applied for attenuation of liver injury following hepatic I/R.     

乙醇诱导脂肪肝过程中肝组织一氧化氮合酶的表达及作用

目的　观察乙醇诱导脂肪肝过程中肝组织一氧化氮合酶 (NOS)的表达 ,探讨不同亚型NOS表达与脂质过氧化的关系。方法　在大鼠饮水中加入乙醇建立乙醇性脂肪肝模型 ,采用免疫组化和逆转录多聚酶链反应 (RT PCR)的方法动态观察肝组织中NOS的蛋白及基因表达 ,同时检测肝组织中一氧化氮 (NO)、丙二醛 (MDA)含量。结果　成功建立乙醇性脂肪肝大鼠模型。与正常对照组相比 ,造模大鼠肝组织在第 4周时诱导型一氧化氮合酶 (iNOS)表达已显著增加 (P <0 .0 5 ) ,第 12周达高峰 ,而后有所下降 ,第 2 0周时又明显上升 (P <0 .0 1)。内皮型一氧化氮合酶 (eNOS)在第 4周时表达无明显改变 (P >0 .0 5 ) ,随造模时间延长而逐渐降低 (P <0 .0 5 )。肝组织中NO水平在第 4周时无明显升高 (P>0 .0 5 ) ,以后显著增加 ,第 12周达高峰 ,而后有所下降 ,第 2 0周时又明显上升 (P <0 .0 1)。肝组织中MDA含量在第 4周已显著升高 (P <0 .0 5 ) ,随饮用乙醇时间延长进行性增加。肝组织中NO、MDA含量与iNOS表达成正相关 (P <0 .0 1) ,与eNOS表达成负相关 (P <0 .0 1)。结论　乙醇诱导脂肪肝过程中肝组织NO水平升高主要与iNOS的活化有关 ,iNOS产生的NO可能与脂质过氧化损伤有关 ,而eNOS产生的NO可能起抗脂质过氧化损伤的保护作用。     

Liposome-mediated gene transfer of endothelial nitric oxide synthase to cirrhotic rat liver decreases intrahepatic vascular resistance

Background and Aims:  Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. The present study evaluates the effects of liposome-mediated gene transfer of eNOS on the intrahepatic vascular resistance and portal venous pressure (PVP) in cirrhotic rats.
Methods:  Hepatic cirrhosis was induced in male Sprague–Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl₄), whereas the control normal rats were given the same dose of peanut oil. Plasmid eukaryotic expression vector (liposome-pcDNA3/eNOS) was injected into the portal vein of CCl₄ cirrhotic rats, whereas cirrhotic controls received the same dose of naked plasmid (liposome-pcDNA3) or Tris buffer, and control normal rats received the same dose of Tris buffer. Five days after gene transfer, the levels of eNOS mRNA and protein, NO production, PVP and the changes of hepatic intrahepatic vascular resistance were investigated.
Results:  Five days after eNOS gene transfer, the levels of eNOS mRNA, eNOS protein and NO production in cirrhotic rats increased remarkably, while hepatic vascular resistance and PVP decreased significantly in cirrhotic rats.
Conclusion:  Liposome-mediated eNOS gene transfer via intraportal injection is feasible and the increase of intrahepatic eNOS leads to a marked decrease in introhepatic vascular resistance and PVP. These data indicate that intrahepatic eNOS plays an important role in the pathogenesis of portal hypertension and gene transfer of eNOS is a potential and novel therapy for portal hypertension.     

缺血预处理对大鼠缺血再灌注后心房肌Cx43和Cx40的影响

目的 探讨缺血预处理对大鼠缺血再灌注后的心房肌缝隙连接蛋白43(Cx43)和缝隙连接蛋白40(Cx40)表达和分布的影响。方法 30只Wistar大鼠随机分为假手术组(或对照组,n=5)：只穿线不结扎左冠状动脉前降支。缺血再灌注组(I/R组,n=5)：给予前降支结扎30 min,再灌注120 min。早期缺血预处理组(IPC组,n=5)：行IPC处理后,余处理同I/R组。延迟IPC组(L-IPC组,n=5)：在IPC处理24h后,余处理同I/R组。早期远程缺血预处理组(RIPC组,n=5)：给予RIPC后,余处理同I/R组。延迟RIPC组(L-RIPC组,n=5)：RIPC处理24h后,余处理同I/R组。测量心房组织Cx40、43的mRNA表达、Cx40、43蛋白表达以及用免疫组化法测定Cx40、43的分布。结果 I/R组Cx43和Cx40在mRNA水平和蛋白水平均明显降低,分布无规律且侧面分布相对增加。而各种IPC方式(IPC、L-IPC、RIPC、L-RIPC)在I/R后,心房Cx43和Cx40mRNA水平和蛋白水平下降不明显,其分布多于心肌细胞闰盘处,仅少量分布于心肌细胞侧面。结论 IPC能维持I/R后的心房肌Cx43和Cx40的较高表达,并维持其空间分布相对稳定。     

Effect of adrenomedullin on hepatic damage in hepatic ischaemia/reperfusion injury in rats

Aims: Adrenomedullin (AM) is a multifunctional peptide with a putative beneficial role after an ischaemic insult. The aim of this study was to evaluate the effect of AM on partial hepatic ischaemia reperfusion (I/R) injury. Methods: Rats were subjected to 1 h of 70% hepatic ischaemia, followed by reperfusion or sham. At the end of ischaemia, vehicle (phosphate‐buffered saline solution), N‐nitro‐l ‐arginine methyl ester (l ‐NAME) and AM with or without l ‐NAME were infused via the portal vein. Analysis was performed at pre‐ischaemia, ischaemia onset and 1, 2 and 4 h after reperfusion. Hepatic tissue blood flow (HTBF) was evaluated by laser Doppler. Results: Plasma AM levels in the I/R groups were significantly lower than the levels in the sham group. AM treatment significantly reduced levels of aspartate transaminase and tissue arginase (P<0.05). Significant decreases of tumour necrosis factor‐α, interleukin‐1β and endothelin‐1 levels were also found in the serum. Endothelin‐1, malondialdehyde and necrosis were observed more frequently in liver tissue in the AM group than the control (P<0.05). Tissue nitric oxide, energy charge and HTBF were significantly increased in AM treatment experiments (P<0.05). Conclusion: The improved HTBF, energy charge and nitric oxide and the reduction of hepatic necrosis, oxidative stress, liver enzymes, endotelin‐1 and pro‐inflammatory cytokines demonstrate that treatment with AM attenuates liver I/R injury.     

辛伐他汀对非酒精性脂肪性肝病大鼠肝组织纤维化的影响及分子机制

目的 探讨辛伐他汀对非酒精性脂肪性肝病(NAFLD)肝组织纤维化模型及肝星状细胞的作用及其分子机制.方法 ①体内实验应用高脂饮食建立NAFLD肝组织纤维化大鼠模型,并用辛伐他汀干预,RT-PCR法和Western印迹检测大鼠肝组织中内皮型一氧化氮合酶(eNOS)、诱导型NOS(iNOS)和Ⅰ型胶原mRNA和蛋白的表达.②体外实验采用促进脂肪细胞分化的培养基诱导人肝星状细胞株LX-2细胞获得静止表型,分别用转化生长因子β1( TGF-β1)、NOS抑制剂亚硝基左旋精氨酸甲酯(L-NAME)、辛伐他汀、TGF-β1+辛伐他汀、L-NAME+辛伐他汀处理静止型LX-2细胞,RT-PCR法和Western印迹检测各组LX-2细胞中eNOS、iNOS、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原mRNA及蛋白的变化.结果 ①随造模时间延长,模型组大鼠肝组织eNOS mRNA和蛋白表达逐渐减少,iNOS和Ⅰ型胶原mRNA和蛋白表达逐渐增加,与正常对照组比较差异有统计学意义(P分别＜0.05和0.01).与24周末模型组相比,辛伐他汀干预组大鼠肝组织eNOS mRNA和蛋白的表达分别增加(0.30±0.02比0.24±0.01和0.45±0.04比0.22±0.02,P值均＜0.05),iNOS mRNA和蛋白的表达分别减少,Ⅰ型胶原mRNA和蛋白表达分别减少(P值均＜0.05).模型组大鼠肝组织中eNOS mRNA和蛋白表达与Ⅰ型胶原mRNA和蛋白表达均呈负相关(P值均＜0.01);iNOS mRNA和蛋白表达与Ⅰ型胶原mRNA和蛋白表达均呈正相关(P值均＜0.01).②体外培养LX-2细胞中,L-NAME能抑制LX-2细胞活化,减少eNOS和iNOS的表达,增加α-SMA和Ⅰ型胶原表达,与TGF-β1作用一致;辛伐他汀能直接增加静止型及活化型LX-2细胞中eNOS的表达,减少iNOS的表达,维持其静止表型,抑制其活化.结论 辛伐他汀通过增加LX-2细胞中eNOS表达,减少iNOS表达,减少α-SMA和Ⅰ型胶原生成,抑制或逆转肝纤维化发生和发展.     

Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial

ObjectiveNovel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC).MethodsThis was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients.Results24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5–419.5 versus 172.5 IU/L IQR 115–298 respectively, p = 0.61). Groups were similar in secondary endpoints.ConclusionThis RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy.     

天麻酚类成分对脑缺血模型大鼠海马一氧化氮和一氧化氮合酶的影响

目的探讨天麻酚类成分对脑缺血大鼠海马NO和一氧化氮合酶(NOS)的影响。方法采用双侧颈总动脉永久性结扎法,造成大鼠脑缺血模型。造模6周后,SD大鼠40只随机分为5组,假手术组、模型组、尼莫地平组、天麻酚类成分高剂量组(高剂量组)和天麻酚类成分低剂量组(低剂量组),每组8只。给药3周后,比色法检测海马NO含量和NOS活性,免疫印记法检测大鼠海马NOS 3种亚型(nNOS,iNOS,eNOS)的表达。结果与假手术组比较,模型组大鼠海马NO含量、NOS活性及nNOS和iNOS表达明显升高,eNOS表达明显降低;与模型组比较,尼莫地平组和高剂量组大鼠海马NO含量、NOS活性及nNOS和iNOS表达明显降低,eNOS表达明显升高;低剂量组大鼠NOS活性和iNOS表达明显降低,差异有统计学意义(P<0.05,P<0.01)。结论天麻酚类成分对脑缺血大鼠海马NO损伤有保护作用。     

内皮型一氧化氮合酶在实验性血管痉挛中的作用

目的 :研究内皮型一氧化氮合酶 (eNOS)与兔实验性血管痉挛的关系。方法 :2 8只新西兰白兔分成假手术对照组 (8只 )、手术加普通饮食组 (8只 )和手术加高胆固醇饮食组 (12只 )。血管造影观察球囊内皮剥脱前后和分别给予普通饮食和高胆固醇饮食喂养 8周后麦角新碱诱发血管痉挛情况。硝酸还原酶法测定各组血浆一氧化氮 (NO)水平 ,免疫组化检测各组血管eNOS含量。结果 :血管造影显示手术加高胆固醇饮食组可诱导出局限性血管痉挛。免疫组化显示eNOS定位在血管内皮细胞胞质、痉挛血管节段内皮细胞内表达减少。手术加高胆固醇饮食组血浆NO的含量也明显下降。结论 :高胆固醇和内皮剥脱使eNOS合成下调 ,血管eNOS含量降低可能与实验性血管痉挛的诱发高度相关     

老年大鼠主动脉对胰岛素敏感性的改变及其机制

目的观察大鼠主动脉对胰岛素敏感性的增龄改变并分析其可能机制。方法老年组采用老年（18月龄）SD大鼠20只,随机选取成年（15周龄）SD大鼠20只为对照组。采用离体血管灌流技术,观察胸主动脉对胰岛素反应性的变化,并同时测定两组主动脉血管一氧化氮（NO）释放量及血管一氧化氮合酶（eNOS）活性;免疫组织化学法及Western Blot法检测老年组及成年组胸主动脉eNOS的蛋白表达变化。结果胰岛素可以浓度依赖性舒张成年大鼠胸主动脉,舒血管作用具有内皮依赖性。与之相比,老年大鼠主动脉对胰岛素的舒张反应显著下降（P<0.05）。同时发现,与成年组相比,老年组NO释放量以及eNOS活性显著降低（P<0.05）,免疫组织化学染色显示老年组主动脉eNOS的蛋白表达显著降低;而Western Blot检测发现老年组血管eNOS磷酸化水平显著降低（P<0.05）。结论血管组织内源性eNOS-NO系统活性下降可能是衰老导致的血管胰岛素敏感性下降的重要机制。     

Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats.

BACKGROUND: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. This study investigated the activity of nitric oxide synthase (NOS) in cirrhosis induced by bile duct-ligation (BDL) with NOS inhibitors. METHOD: Three days after operation, rats were randomized to receive aminoguanidine (AG, 25 mg/kg/day) or L-N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) for 21 days. RESULTS: Vascular NO production, which was increased in BDL cirrhotic rats, was reduced by 75% with AG but not L-NAME chronic administration. AG treatment attenuated liver damage, while L-NAME aggravated it. AG significantly suppressed inducible NOS (iNOS) expression in aorta of BDL rats at both mRNA and protein level, but much less efficient in reducing it in liver. In contrast, endothelial NOS (eNOS) expression was not markedly affected. Calcium-independent NOS activity, which was dramatically increased in aorta of BDL rats, was abolished by AG treatment. In liver, however, both calcium-dependent and -independent NOS activity were increased by AG treatment. CONCLUSION: Chronic administration of AG could reduce systemic NO levels as well as suppress iNOS expression and activity in aorta of BDL rats. It also improved liver function, possibly because of its ability to increase hepatic NOS activity, and to correct the systemic hemodynamic disorders by decreasing vascular NO production.     

庚醇预处理的心脏保护作用对细胞膜缝隙连接蛋白43的影响

目的探讨庚醇预处理对家兔心肌缺血再灌注损伤的作用及其机制。方法将50只新西兰大白兔随机分为5组:假手术组、缺血再灌注组(IR组)、缺血预处理组(IP组)、庚醇预处理组(HP组)、庚醇预处理加5-羟葵酸(5-HD)预处理组(HP+5-HD组),每组10只。所有新西兰大白兔再灌注4h后处死。分别于术前、缺血时、再灌注2、4h检测血浆肌酸激酶同工酶和心肌肌钙蛋白活性;采用免疫荧光标记检测Cx43。结果与IR组比较,IP组及HP组心肌坏死区/左心室范围明显降低(P<0.01)。与假手术组比较,IR组、HP+5-HD组Cx43mRNA表达明显降低(P<0.01);与HP+5-HD组比较,IP组、HP组Cx43mRNA表达明显升高(P<0.01);与IR组比较,IP组、HP组、HP+5-HD组Cx43mRNA表达明显升高(P<0.05,P<0.01)。结论庚醇预处理可以通过衰减由心肌缺血再灌注诱导的细胞膜Cx43表达下降,对损伤心肌起到保护作用。     

内皮型一氧化氮合酶基因多态性与原发性高血压的相关关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因27bp数目可变的串联重复序列(VNTR)多态性与中国汉族人原发性高血压(EH)的相关性。方法 (1)聚合酶链反应(PCR)及琼脂糖凝胶电泳检测334例EH患者的基因型，同时进行基因测序。(2)硝酸还原酶法测定空腹血清一氧化氮代谢物(NOx)水平，用放射免疫法测定内皮素(ET)的水平。结果(1) EH组aa ab基因型和a等位基因频率显著高于对照组；(2)EH组内ab ab基因型空腹血清NOx、NOx／ET比明显低于bb基因型。结论 eNOS基因27bpVNTR的a等位基因与中国汉族人EH的发生相关，a等位基因携带者可能通过减少内皮：NO的释放、损害内皮功能参与EH发病。