Response of blood endothelin-1 and nitric oxide activity in duodenal ulcer patients undergoing Helicobacter pylori eradication

AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively enrolled to receive one-week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one-month rabeprazole therapy. They were asked back to determine ulcer and Hpylori status using endoscopy one month later. Thirty-seven healthy controls (H pylori +/-:17/20) were enrolled for comparison. Blood samples were collected in each visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The ulcer healing and Hpylori-eradication rates were 86.7% and 83.3%, respectively. Plasma ET-1 level in DU patients was higher than that of Hpylori-negative and positive controls (3.59±0.96 vs0.89±0.54 vs0.3±0.2 pg/mL,P<0.01), while nitrate/nitrite levels among them were also significantly different (8.55±0.71 vs5.27±0.68 vs 6.39±0.92 μmol/L, P<0.05). H pylori eradication diminished ET-1 levels (3.64±0.55 vs2.64±0.55 pg/mL, P<0.01) but elevated nitrate/ nitrite level (8.16±0.84 vs11.41±1.42 umol/L,P<0.05). CONCLUSION: Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After an effective H pylori eradication, DU healing is associated with diminished blood ET-1 level and elevated nitrate/nitrite level.

Influence of moxibustion temperatures on blood lipids, endothelin-1, and nitric oxide in hyperlipidemia patients

OBJECTIVE： To observe the influence of moxibustion temperature on blood lipids, endothelin-1（ET-1）, nitric oxide（NO）, and ET-1/NO in hyperlipidemia patients. METHODS： Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS： Total cholesterol and triglyceride, were lower in the treatment group than in the control group（P0.05）. Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group（P0.001）. Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION： Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.

INHIBITION OF NITRIC OXIDE SYNTHESIS INCREASES THE SECRETION OF ENDOTHELIN-1 IN VIVO AND IN CULTURED ENDOTHELIAL CELLS

The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 ?3.1 kPa and 68.7 ?10.2 kPa.s / L respectively. IG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 ?4.7 kPa and 158.4 ?25 kPa.s / L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin? level in the femoral artery increased by 20.9+ 7.1, 25.6?7.7, 28.6?7.9 pg / ml at the 60 th, 120th, 180th minute after the injection of L-NAME respectively (P<0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 ?.9 pg / 105 cells /ml (n=9). L-NAME increased endothelin-1 level to 42.8 ?4.9pg / 105 cells / ml (n = 9, P < 0.05) in case of 10-11 mol / L and to 43.0+ 4.7 pg / 105 cells / ml in case of 10 -7 mol/L (n=9, F<0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin? in vivo and in cultured vascular endothelial cells.

Murine study of portal hypertension associated endothelin-1 hypo-response

AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.

Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate

The effect of hyperlipidemia and inflammation on endothelial functions was studied.The enrolled included control(basic chow),hyperlipidemia and fenofibrate-treated groups(high fat diet).The hyperlipidemia model was set up by four-week atherogenic diet,followed by a 16-week treat-ment in the fenofibrate-treated group(fenofibrate 40 mg/kg every day)and without treatment in the hyperlipidemia group,respectively.In the 20th week,serum lipid level and NO levels were measured,and the expression of vascular cell adhesion molecule-1(VCAM-1)and cell adhesiveness in aortic endothelia observed by computer-aided system.Com-pared with the control group,hyperlipidemia rats showed lower levels of NO and increases in leukocyte accumulation on the endothelial surface,also stronger and more extensive endothelial expression of VCAM-1.In fenofibrate-treated group,the expression of VCAM-1 and leukocyte accumula-tion on the endothelial surface was decreased,while serum levels of NO were increased as compared with hyperlipidemia group.Hyperlipidemia can inhibit the NO activity and pro-mote the damage of VACA-1 to aortic endothelia.Fenofibrate can effectively prevent the pathogenesis of atherosclerosis by restoring NO levels and down-regulating the VCAM-1 expression.

Polymorphism of the endothelin-1 gene(rs5370)is a potential contributor to sickle cell disease pathophysiology

Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals,the variability highlighted by differing genetic haplotypes.Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase(eNOS)and endothelin-1(ET-1)genes,the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear.To deconvolute their potential significance among African Americans with sickle cell disease,we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease(n Z 331)and control(n Z 379)groups,with a polymerase echain reaction restriction fragment length polymorphism assay.We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups.eNOS homozygote mutants,which had been shown to have clinical significance elsewhere,showed no statistical significance in our study.On the other hand,and contrary to previous report among Africans with sickle cell disease,the endothelin-1 homozygous mutant variant showed significant difference in genotypic(p Z 2.84E-12)and allelic frequencies(p Z 2.20E-16)between groups.The most common haplotype is the combination of T786C homozygote wildtype variant with homozygote mutant variants of G5665T(ET-1)and Glu298Asp(eNOS).These results show that endothelin-1(rs5370)polymorphism,rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease.This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.

Serum and lung endothelin-1 increased in a canine model of ventilator-induced lung injury

Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin-1 （ET-1） and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume （VT） mechanical ventilation, which included a VT6 group （VT equaled to 6 ml/kg body weight, positive end expiratory pressure （PEEP） equaled to 10 cmH20, n=-6）, a VT10 group （VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4） and a VT20 group （VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6） for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation （P 〈0.05） while the serum NO levels were similar in the three groups （all P 〉0.05）. There was no significant difference in serum ratio of ET-1/NO between any two out of three groups （P 〉0.05）, although there was a significant positive relationship between serum ET-1 and serum NO （r=0.80, P 〈0.01）. The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group （both P 〈0.05） while there was no significant difference in lung NO levels between two groups （P〉0.05）. In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation （P 〈0.05） as there was a significant positive relationship between ET-1 and NO in the lung （r=0.54, P 〈0.05）. Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.

Effects of Liandou Qingmai Recipe(连豆清脉方) on Endothelin-1,Nitric Oxide,Interleukin-6 and Interleukin-10 Levels in Patients with Coronary Heart Disease

Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.

麦绿素对实验性高脂血症大鼠血脂及MDA、SOD、ET-1、NO的影响

研究麦绿素对食饵性高脂血症大鼠血脂及血浆丙二醛(MDA)、超氧化物歧化酶(SOD)、内皮素1(ET-1)、一氧化氮(NO)的影响。SD大鼠32只,随机均分为四组,即正常八周对照组(8NC)、高脂模型八周组(8HF)、高脂模型四周后再加低剂量麦绿素治疗四周组(BG-L)和高脂模型四周后再加高剂量麦绿素治疗四周组(BG-H)。检测大鼠血脂及血浆MDA、SOD、ET-1、NO的变化。结果表明,麦绿素治疗组同高脂模型八周组比较,血浆总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的含量降低,高密度脂蛋白胆固醇(HDL-C)的含量升高;血浆SOD活性和NO含量明显升高,而MDA和ET-1含量明显降低;提示麦绿素具有降血脂、抗氧化和改善血管内皮功能的作用。

非诺贝特对高脂血症大鼠NO及血管内皮细胞粘附分子-1表达的影响

目的探讨血脂与炎性因子对内皮功能的损伤机制。方法实验包括正常对照组(基础饲料喂养),高脂血症组(高脂喂养)和高脂血症非诺贝特治疗组(高脂喂养),其中非诺贝特治疗组在高脂喂养同时喂服非诺贝特40mg·(kg-1·d-1)而高脂血症组不予药物治疗,20周后检测3组的血脂、NO浓度及观察血管内皮血管细胞粘附分子-1(VCAM-1)的表达水平和细胞粘附密度。结果与正常对照组比较,高脂血症组NO水平较低、血管内皮上白细胞粘附增多、VCAM-1表达强度较强及范围较广。非诺贝特治疗组与高脂血症组比较,血NO水平提高、血管内皮VCAM-1表达水平和细胞粘附数目均较低(少)。结论NO减少及炎症因素的介入参与了血管损害机制,非诺贝特能有效地阻止动脉硬化的发生,该作用与NO水平提高、VCAM-1表达下调有关。

高脂血症对内皮VCAM-1表达的影响及非诺贝特的血管保护作用

目的探讨血脂与炎性因子在动脉硬化早期对内皮功能的损伤机制。方法实验包括正常对照组(只喂基础饲料),另两组通过4周建立高脂血症模型,以后继续高脂喂养,其中非诺贝特治疗组在高脂喂养同时喂服非诺贝特40mg/(kg.d),而高脂血症组不予药物治疗,20周后检测3组的血脂、一氧化氮浓度及观察血管内皮VCAM-1的表达水平和细胞黏附密度。结果与正常对照组比较,高脂血症组NO水平较低、血管内皮上白细胞黏附增多、VCAM-1表达强度较强及范围较广。非诺贝特治疗组与高脂血症组比较,血NO水平提高、血管内皮VCAM-1表达水平和细胞黏附数目均较低(少)。结论高脂血症可抑制机体NO活性,并促进VCAM-1对血管内皮的损害,非诺贝特能有效地阻止动脉硬化的发生,该作用与一氧化氮水平提高、VCAM-1表达下调有关。

高脂状态对大鼠动脉血管紧张素Ⅱ1型受体mRNA及一氧化氮的影响

目的观察高脂饮食对大鼠动脉血管紧张素Ⅱ1型受体(angiotensinⅡ1,AT1)mRNA表达、血清一氧化氮(nitrogen monoxidum,NO)水平的影响及降脂治疗的作用,探讨高脂饮食诱导内皮功能障碍的可能机制。方法将30只SD大鼠按电脑数字随机法分为3组,每组10只:正常对照组、高脂血症组和高脂血症治疗组。高脂血症组持续高脂喂养,高脂血症治疗组4周后在高脂喂养同时喂服辛伐他汀10mg/(kg·d),高脂血症组不予药物治疗。第20周末检测3组的血清脂蛋白浓度及AT1mRNA表达水平、血清AngⅡ和NO浓度。结果高脂血症组和高脂血症治疗组第4周末血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇浓度均高于正常对照组,差异有统计学意义(P>0.05)。第20周末,高脂血症治疗组血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇浓度低于高脂血症组差异有统计学意义(P>0.05)。3组第20周末收缩压比较,差异无统计学意义[(126±14)mm Hg vs.(127±13)mm Hg vs.(125±13)mm Hg,P>0.05;1mm Hg=0.133kPa]。方差分析显示,3组第20周末血清NO2-/NO3-浓度[(38.0±9.9)μmol/L vs.(29.6±7.2)μmol/L vs.(35.8±9.5)μmol/L,P<0.05]、主动脉组织AT1mRNA表达水平(0.66±0.05vs.0.75±0.08vs.0.70±0.06,P<0.05]差异有统计学意义;3组血清AngⅡ浓度比较差异无统计学意义(P>0.05)。相关分析结果显示,AT1mRNA表达水平与血清总胆固醇、三酰甘油浓度呈显著正相关(r=0.708,P<0.05;r=0.656,P<0.05)。结论高脂可能通过上调AT1受体表达和抑制NO活性而损伤血管,他汀类药物则可逆转这种状态,有利于阻止动脉硬化的发生发展。

The NO/ET-1 System Is Involved in the Protection of the Hepatic Ischemic Preconditioning

To study the relationship between the disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the hepatic ischemia/reperfusion (I/R) injury as well as the regulation of the NO/ET-1 system by the hepatic ischemic preconditioning (IPC), the changes of the NO/ET-1 system and their relationship with the hepatic I/R injury were compared between the I/R group and the IPC+I/R group in a rat hepatic I/R model. 2 h after reperfusion, the liver tissues were examined for expressed inducible nitric oxide synthase (iNOS) mRNA by RT-PCR. In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to the significant reduction of NO - 2/NO - 3 (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and level of MDA in liver tissue were increased but ATP in liver tissue was reduced, and the hepatic damage was deteriorated. The protection of the hepatic IPC was associated with the elevated ratio of NO/ET-1 caused by the elevation of NO - 2/NO - 3, and reduction of ET-1 as well. No iNOS mRNA was detected in the liver tissues. It was concluded that hepatic I/R injury was related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be mediated by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this scenario.

Effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis

Objective:To study the effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis.Methods: Patients diagnosed with periodontitis in our hospital between May 2013 and March 2016 were selected to screen 72 cases of smokers and 80 cases of non-smokers who were enrolled in smoking group and non-smoking group respectively, periodontal tissue was collected to detect the expression of EA, NOS and NLRP3 inflammasome, and gingival crevicular fluid was collected to detect the content of ET-1, NO, inflammatory factors and MMPs.Results:EA expression and ET-1 content in gingival tissue of smoking group were significantly higher than those of non-smoking group while NOS expression and NO content in gingival tissue were significantly lower than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression in gingival tissue of smoking group were significantly higher than those of non-smoking group, and IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content in gingival crevicular fluid were significantly higher than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression as well as IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content were positively correlated with EA and ET-1, and negatively correlated with NOS and NO.Conclusion:Smoking can cause increased EA and ET-1 as well as decreased NOS and NO in gingival tissue of patients with chronic periodontitis, thus adjusting the expression of NLRP3 inflammasome and MMPs to periodontal tissue inflammation and structure damage.

Preventive effects of geranylgeranylacetone on rat ethanolinduced gastritis

AIM:To establish a rat ethanol gastritis model,we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.METHODS:One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups:normal control group,undergoing gastric perfusion of normal saline(NS) by gastrogavage;model control group and 2 model therapy groups that underwent gastric perfusion with ethanol(distillate spirits with 56% ethanol content) by gastrogavage for 4 wk.Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups,while the same amount of NS,instead of geranylgeranylacetone was used in that model control group.The rats were then sacrificed and stomachs were removed.The injury level of the gastric mucosa was observed by light and electron microscopy,and the levels of prostaglandin 2(PGE 2),endothelin-1(ET-1) and nitric oxide(NO) were measured by radioimmunoassay and the Griess method.RESULTS:The gastric mucosal epidermal damage score(EDS;4.5) and ulcer index(UI;12.0) of the model control group were significantly higher than that of the normal control group(0 and 0 respectively,all P = 0.000).The gastric mucosal EDS and UI of the 2 model therapy groups(EDS:2.5 and 2.0;UI:3.5 and 3.0) were significantly lower than that of the model control group(all P < 0.01).There was no statistically significant difference between the low-dose and high-dose model therapy groups.The expression value of plasma ET-1 of the model control group was higher than that of the normal control group(P < 0.01) and the 2 model therapy groups(all P < 0.01).The expression values of gastric mucosal PGE 2 and serum NO of the model control group were lower than those of the normal control group(all P < 0.05) and the 2 model therapy groups(all P < 0.05).The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group(all P < 0.01) and the 2 model therapy groups(all P < 0.05).Scanning and transmission electron microscopy observation showed that in the model control group,the epithelial junctions were vague,the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group.However,in the 2 model therapy groups,damage to the intercellular joints and organelles was ameliorate relative to the model control group.CONCLUSION:Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion.The mechanism could be related to regulation of ET-1,NO and PGE 2.

Shallow needling on Neiguan and Gongsun acupoints in rats with brain ischemia Changes in apoptosis regulating genes and vasoactive substances

For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan （PC 6） and Gongsun （SP 4） acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.

高血压病血管内皮功能障碍及治疗

内皮细胞功能障碍是近年来的热门研究课题,从基础到临床受到广泛重视。高血压是发病率最高的心血管疾病,其发病环节与内皮细胞功能关系密切,二者均是心脑血管事件链中的重要环节。本文回顾了多种内皮因子的功能及其与高血压的关系,高血压病内皮功能障碍的可能机制,肱动脉超声检查方法以及内皮功能障碍的治疗对策。

化痰通络汤预先灌胃的合并高脂血症脑缺血大鼠神经系统功能、脑组织病理变化观察

目的观察化痰通络汤预先灌胃的合并高脂血症脑缺血大鼠神经系统功能及脑组织病理变化,并探讨其可能作用机制。方法 70只大鼠予高脂饲料喂养6周,制作高脂血症模型,将大鼠随机分为高脂血症对照组(正常组) 15只、高脂血症假手术组(假手术组) 15只、高脂血症合并脑缺血组模型组(模型组) 20只、治疗组20只,饲养第7周开始,治疗组予化痰通络方1. 330 g/(kg·d)灌胃处理,正常组、假手术组和模型组予等体积生理盐水,连续4周,每天1次。饲养第9周模型组、治疗组采用线栓法建制备脑缺血模型,假手术组手仅分离不结扎血管。正常组大鼠不做任何处理。饲养11周时,评定模型组、治疗组大鼠神经系统功能,处死大鼠取脑组织,计算脑梗死体积比。饲养11周时取各组大鼠,处死后取脑组织,采用ELISA法检测各组脑组织一氧化氮(NO)、血管内皮素-1(ET-1)和血管性血友病因子(v WF),免疫组化法检测脑组织血管内皮生长因子(VEGF)、CD34。结果治疗组与模型组大鼠神经功能评分分别为(1. 63±0. 20)、(3. 11±0. 22)分,二者比较,P <0. 05。治疗组与模型组大鼠脑梗死体积比分别为16. 82%±7. 18%、32. 97%±9. 86%,二者比较,P <0. 05。与正常组、假手术组比价,模型组脑组织ET-1和v WF含量增加(P均<0. 05),治疗组脑组织NO、ET-1和v WF含量增加(P均<0. 05)。与模型组比较,治疗组脑组织NO含量增加、ET-1和v WF含量均降低(P均<0. 05)。与正常组、假手术组比较,模型组、治疗组脑组织VEGF和CD34阳性表达量均升高(P均<0. 05);与模型组相比,治疗组脑组织VEGF和CD34阳性表达量增加(P均<0. 05)。结论化痰通络汤预先灌胃的合并高脂血症脑缺血大鼠的神经系统功能降低、脑梗死体积减少,其机制可能为促进脑组织NO、VEGF、CD34表达,降低ET-1和v WF含量。

吉非罗齐对高脂血症鼠一氧化氮活性及血管内皮粘附的影响

探讨高脂血症在动脉硬化早期对内皮功能的损伤机制。实验分为对照组、高脂血症组和吉非罗齐治疗组 ,对照组只喂基础饲料 ,另两组通过 4周建立高脂血症模型 ,此后继续高脂喂养 ,其中吉非罗齐治疗组在高脂喂养同时喂服吉非罗齐 6 0mg (kg·d) ,16周后检测三组的总胆固醇、甘油三酯、一氧化氮浓度以及观察血管内皮血管细胞粘附分子 1的表达水平和细胞粘附密度。结果发现 ,与对照组比较 ,高脂血症组一氧化氮水平降低 ,血管细胞粘附分子 1表达强度增强及范围较广 ,且白细胞粘附数明显增多。与高脂血症组比较 ,吉非罗齐治疗组血清一氧化氮水平增高、血管细胞粘附分子 1表达水平降低和白细胞粘附数减少。结果提示 ,高脂血症抑制机体一氧化氮活性 ,并促进血管细胞粘附分子 1对血管内皮的损害 。

超声联合一氧化氮微泡对大鼠心肌组织的生物学效应

目的:本研究旨在探讨超声联合一氧化氮(NO)微泡的作用对大鼠心肌组织局部基质衍生因子-1(SDF-1)的影响,及其对心肌组织作用的安全性。方法:将32只SPF级SD雄性大鼠随机分为4组,每组8只。第1、2、3组分别经尾静脉输入1 ml的NO微泡、普通脂质微泡以及PBS,并采用频率为1 MHz、强度为1 W/cm2的超声辐照大鼠心前区,辐照时间为10 min;第4组为空白对照组。4 h后每组处死4只大鼠,留取心肌组织进行HE染色,观察局部的炎症反应情况;同时留取血清标本用于检测肌酸激酶(CK),乳酸脱氢酶(LDH)和肌钙蛋白I(TnI)的含量。1周后处死剩余大鼠,取心肌组织进行RT-PCR和Western blot分别检测SDF-1的基因及蛋白相对表达量。结果:辐照4 h后留取心肌组织行HE染色显示各组均可见少量炎性细胞浸润,组间没有明显差异;血清学指标检测显示,第1组与第2组血清CK和LDH高于第3组和第4组,且差异有统计学意义(P<0.05);第1组血清TnI低于第2组,但高于第3组和第4组,且差异有统计学意义(P<0.05);辐照1周后留取的心肌组织行RT-PCR和Western blot分析结果均显示第1组SDF-1相对表达量最多,各组间进行两两比较,差异均有统计学意义(P<0.05)。结论:超声联合NO微泡辐照大鼠心肌组织,与内含全氟显气体的普通脂质微泡一样,对心肌组织无明显破坏;但能使大鼠心肌组织SDF-1表达增加,其程度高于应用超声联合普通脂质微泡,因此,NO微泡应用于干细胞归巢将优于目前普通脂质微泡。