Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.

Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center,strongly associated with H pylori infection.The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS:We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls.A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM- 1 and integrin β7.In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated.We also performed immunostaining with anti-CD20,CD4,CD8 and CD68 antibodies to determine the lymphocyte subsets co- expressing integrin β7. RESULTS:Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection.Of note,the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls.Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates.Integrin β7-expressing mononuclear cells,mainly composed of CD20 and CD4 lymphocytes,were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM一1/ integrin a4p7 homing system may participate in gastric inflammation in response to H py/o}i-infection and contributes to MALT formation, typically leading to the development of NG.

The Role of Endoplasmic Reticulum Stress-related Apoptosis in Vascular Endothelium Pathogenesis

Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

Effects of PAF and PAF antagonist WEB 2170 on relaxation of vascular endothelium after brief deoxygenation and reoxygenation

By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min of reoxygenation, to 36. 1% of norepinephine(NE) precontraction. PAF receptor antagonist WEB 2170 markedly improved the Ach-induced relaxation of the brief deoxygenated and reoxygenated rings to 86. 7 % of NE precontraction. The results indicated that PAF may be one of the mediators involved in the endothelium relaxation dysfunction related to brief deoxygenation and reoxygenation, and that PAF antagonist WEB 2170 has the protective effect on endothelium relaxation function.

Clinical effect of Calcium Dobesilate combinated with Alprostadil in the vascular endothelium of patients with diabetic nephropathy

Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.

Effects of α-lipoic acid on oxidative stress, vascular endothelium function and renal function in patients with diabetic nephropathy

Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.

Effect of Huangqi Xiaoke Recipe combined with alprostadil on qi and yin deficiency type diabetic nephropathy and its effect on vascular endothelium and oxidative stress

Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.

Zinc(Ⅱ)metal-organic framework eluting titanium implant as propulsive agent to boost the endothelium regeneration

The advent of antiproliferative drug-eluting vascular stents can dramatically reduce in-stent restenosis via inhibiting the hyperproliferation of vascular smooth muscle cells.However,the antiproliferative drugs also restrain the repair of the injured endothelial layer,which in turn leads to the very later in-stent restenosis.Evidence points that competent endothelium plays a critical role in guaranteeing the long-term patency via maintaining vascular homeostasis.Boosting the regeneration of endothelium on the implanted vascular stents could be rendered as a promising strategy to reduce stent implantation complications.In this regard,bioactive zinc(II)metal-organic framework modified with endothelial cell-targeting Arg-Glu-Asp-Val peptide was embedded in poly(lactide-co-caprolactone)to serve as a functional coating on the surface of titanium substrate,which can promote the proliferation and migration of endothelial cells.The in vitro cell experiments revealed that the zinc(II)metal-organic framework embedded in the polymer coating was able to modulate the behaviors of endothelial cells owing to the bioactive effects of zinc ion and peptide.Our results confirmed that zinc(II)metal-organic framework eluting coating represented a new possibility for promoting the repair of the damaged endothelium with potential clinical implications in vascular-related biomaterials and tissue engineering applications.

Hydroxysafflor Yellow A Promotes Vascular Endothelial Cell Proliferation via VEGF/VEGF Receptor

Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.

补阳还五汤干预急性心肌梗死疾病机制的研究进展

急性心肌梗死(AMI)是一种急性发作的冠脉综合征,已成为严重影响人类生活健康的重大疾病,中医药对AMI具有较好的治疗效果,近年来补阳还五汤干预AMI的作用成为了研究的热点。现代药理学研究表示补阳还五汤具有抗血栓、保护血管、抗炎症和抑制细胞凋亡的作用,补阳还五汤具有多靶点,多通路全方位治疗的优点。从保护血管内皮、促进血管生成、抑制心肌重构、抑制炎症因子、抑制细胞凋亡等方面对补阳还五汤干预AMI的研究进展进行综述,为AMI的中医药诊疗研究提供文献依据。

非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者的效果

目的:观察非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者的效果。方法:选取2020年2月至2023年3月该院收治的120例高脂血症合并高尿酸血症患者进行前瞻性研究,按照随机数字表法将其分为对照组和观察组各60例。对照组予以阿托伐他汀钙治疗,观察组在对照组基础上联合非布司他治疗。比较两组临床疗效、治疗前后血脂指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]水平、血尿酸水平、血管内皮功能指标[可溶性细胞间黏附分子-1(sICAM-1)、内皮素-1(ET-1)]水平和不良反应发生率。结果:观察组治疗总有效率为93.33%(56/60),高于对照组的80.00%(48/60),差异有统计学意义(P<0.05);治疗后,观察组TG、TC、LDL-C、血尿酸水平均低于对照组,HDL-C水平高于对照组,差异有统计学意义(P<0.05);观察组sICAM-1、ET-1水平均低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者可提高治疗总有效率,改善血脂指标水平,降低血尿酸和血管内皮功能指标水平,效果优于单纯阿托伐他汀钙治疗。

Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

Serum vascular endothelial growth factor is a potential biomarker of metastatic recurrence after curative resection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. To date, surgery is still the best solution to it. However, metastatic recurrences after curative hepatic resections are very common. Tang et al have reported that recurrence rate within 5 years of curative hepatic resection is 61.5% [1]. As curative hepatic resection has a high tendency for metastatic recurrence, therapeutic interventions such as transarterial embolization and antiangiogenesis have been tried to further improve prognosis of HCC patients. Therefore, establishing a dependable, sensitive, easy, and economical method to predict metastatic recurrence following curative hepatic resection is of clinical urgency.

Reduction of tumorigenicity of SMMC-7721 hepatoma cells by vascular endothelial growth factor antisense gene therapy

AIM: To test the hypothesis to block VEGF expression of SMMC-7721 hepatoma cells may inhibit tumor growth using the rat hepatoma model. METHODS: Amplify the 200 VEGF cDNA fragment and insert it into human U6 gene cassette in the reverse orientation transcribing small antisense RNA which could specifically interact with VEGF165, and VEGF121 mRNA. Construct the retroviral vector containing this antisense VEGF U6 cassette and package the replication-deficient recombinant retrovirus. SMMC-7721 cells were transduced with these virus and positive clones were selected with G418. PCR and Southern blot analysis were performed to determine if U6 cassette integrated into the genomic DNA of positive clone. Transfected tumor cells were evaluated for RNA expression by ribonuclease protection assays. The VEGF protein in the supernatant of parental tumor cells and genetically modified tumor cells was determined with ELISA. In vitro and in vivo growth properties of antisense VEGF cell clone in nude mice were analyzed. RESULTS: Restriction enzyme digestion and PCR sequencing verified that the antisense VEGF RNA retroviral vector was successfully constructed.After G418 selection, resistant SMMC-7721 cell clone was picked up. PCR and Southern blot analysis suggested that U6 cassette was integrated into the cell genomic DNA. Stable SMMC-7721 cell clone transduced with U6 antisense RNA cassette could express 200 bp small antisense VEGF RNA and secrete reduced levels of VEGF in culture condition. Production of VEGF by antisense transgene-expressing cells was 65+/-10 ng/L per 10(6) cells, 42045 ng/L per 10(6) cells in sense group and 485+/-30 ng/L per 10(6) cells in the negative control group, (P【 0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S.C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with control cells. CONCLUSION: Expression of antisense VEGF RNA in SMMC-7721 cells could decrease the tumorigenicity, and antisense-VEGF gene therapy may be an adjuvant treatment for hepatoma.

脂肪酸氧化和促分解脂质介质水平与阴茎勃起功能障碍的相关性研究

目的探究脂肪酸氧化和促分解脂质介质水平与阴茎勃起功能障碍的相关性。方法选取2022年10月—2023年4月新疆医科大学第一附属医院泌尿中心诊治的勃起功能障碍患者70例作为观察组,另外选取同期健康男性70例作为健康对照组。比较2组受试者一般临床资料、血清睾酮(T)、勃起硬度评分(EHS)、阴茎单侧动脉最大收缩期血流速度(PSV)、血清过氧化脂质(LPO)、消退素D1(RvD1)及消退素E1(RvE1)的表达水平。通过相关性分析、多因素Logistic回归分析筛选勃起功能障碍发生的危险因素。进一步通过受试者工作特征曲线(ROC)及曲线下面积(AUC)评价各危险因素对勃起功能障碍发生的预测价值。结果观察组患者血清LPO显著高于健康对照组(t/P=8.714/<0.001),RvD1、RvE1及EHS评分、PSV水平均显著低于健康对照组(t/P=10.109/<0.001、10.410/<0.001、6.271/<0.001、13.243/<0.001);Pearson相关性分析表明,血清LPO水平与EHS、PSV呈负相关(r/P=-0.275/0.033、-0.233/0.049),RvD1及RvE1水平与EHS、PSV呈正相关(r/P=0.391/<0.001、0.366/<0.001、0.423/<0.001、0.387/<0.001);多因素Logistic回归分析表明,血清LPO水平升高是勃起功能障碍发生的独立危险因素[OR(95%CI)=1.127(1.045~1.216)],RvD1及RvE1水平升高均是勃起功能障碍发生的保护因素[OR(95%CI)=0.761(0.669~0.866)、0.787(0.707~0.876)];ROC曲线分析表明,血清LPO、RvD1及RvE1预测勃起功能障碍发生的效能均较高,三者联合预测疾病的价值高于各指标独立预测价值(Z/P=1.873/0.013、1.803/0.019、1.711/0.033)。结论血清脂肪酸氧化水平增高、促分解脂质介质水平降低是勃起功能障碍发生的危险因素,为进一步探究勃起功能障碍的发生、发展机制提供新的思路。

Molecular signal transduction in vascular cell apoptosis

Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.

Beneficial effect of berberine on atherosclerosis based on attenuating vascular inflammation and calcification

OBJECTIVE To investigate the beneficial effect of berberine(BBR)on atherosclerosisin Apo^(-/-) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in human umbilical vein endothelial cells(HUVECs) and smooth muscle cells(SMCs).METHODS 48 Apo-/-E mice,at 6-8 weeks old,were randomly allocated into 4 groups:normal,model,bbr and atorvastatin(positive control) groups with 12 mice in each group.They were fed with high-fat diet for 4 weeks except those in Normal group and then treated with indicated drugs orsolvent for another 4 weeks.The morphology and inflammation infiltration of aortic were examined with HE staining.The expression of BMP-2 in aortic was examined by immumohistochemical staining.Blood lipid levels were examined by automatic biochemical analyzer.The expression of IL-6,TNF-α and BMP-2 in serum and tissues was detected by ELISA method.The expression of ALP and the content of calcium were detected by commercially-available kits.HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24 h.The contents of intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule(VCAM-1),matrix metalloprotein-9(MMP-9) in the culture supernatant were detected by ELISA method.Calcification was induced with β-glycerophosphatein SMC cells and the effect of BBR on the content of calcium was examined.RESULTS 4-week berberine treatment markedly lowered serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P<0.05 or P<0.01) which was comparable with the effect of atorvastatin.Berberineal so significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues(P<0.05 or P<0.001).Berberine tended to decrease ALP,BMP-2 levels and the content of calcium in mice serum and aortic tissues(P<0.05,P<0.01 or P<0.001) which were not observed in atorvastatin group.Berberine significantly lowered the levels of ICAM-1,VCAM-1,and MMP-9 in TNF-α-stimulated HUVECs.It can also lowered the content of calcium in SMCs.CONCLUSION BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet,decrease the injury caused by inflammation,and attenuate vascular calcification.It may improve atherosclerosis and play a role in cardiovascular protection.

探讨丹芪精颗粒对急性高原暴露下肺血管内皮的保护作用

目的运用网络药理学结合临床试验探究阐明丹芪精颗粒对急性高原暴露后肺血管内皮的保护作用。方法首先利用中药系统药理数据库及分析平台(TCMSP)平台检索丹芪精颗粒的有效成分和药物作用靶点,并检索疾病作用靶点,获得疾病与药物的相互作用靶点。随后进行疾病和药物交叉靶点的基因本体论(GO)富集和京都基因与基因组百科全书(KEGG)通路分析,最后构建药物-疾病通路靶标网络图。根据随机对照法将80例患者分为红景天胶囊对照组和丹芪精颗粒组,各40例。分别于两组研究对象不同时间点(进驻高原后第1、3和7天)记录血清血管内皮生长因子(VEGF)和内皮素-1(ET-1)水平。结果网络药理学分析结果显示,丹芪精颗粒可能通过调节急性高原暴露中的VEGF信号通路参与炎症反应等生物学过程。临床试验结果显示,与红景天胶囊组相比,丹芪精颗粒组的VEGF水平升高(F=8.977,P<0.05),ET-1水平降低(F=5.248,P<0.05)。结论丹芪精颗粒对急性高海拔暴露具有多靶点、多通路的治疗作用,并且可以提高急性高海拔暴露患者血管内皮功能核心靶点VEGF水平、降低ET-1动态水平,对肺血管内皮细胞起保护作用。

Effect of calcitonin gene-related peptide-induced preconditioning on attenuated endothelium-dependent vasorelaxation induced by lysophosphatidylcholine

目的：研究降钙素基因相关肽（ＣＧＲＰ）诱导预适应对溶血磷脂酰胆碱（Ｌｙｓ）抑制内皮依赖性舒张的作用．方法：用苯福林收缩兔与大鼠离体胸主动脉环，观察Ｌｙｓ对乙酰胆碱（ＡＣｈ）所致内皮依赖性舒张的影响．结果：ＣＧＲＰ预处理兔和大鼠离体胸主动脉环显著减轻Ｌｙｓ对ＡＣｈ舒血管效应的抑制，其作用可被蛋白激酶Ｃ（ＰＫＣ）抑制剂Ｈ７所取消．结论：ＣＧＲＰ诱导预适应对所致内皮细胞损伤具有拮抗作用，此作用与激活ＰＫＣ有关．