榛蘑多糖对乙醇所致大鼠血管内皮细胞损伤的保护作用

探究榛蘑多糖对乙醇所致大鼠血管内皮细胞损伤的保护作用。将40只SD大鼠随机分成4组(正常对照组、损伤组、榛蘑多糖低剂量组、榛蘑多糖高剂量组)。除正常对照组外的其余各组均按10 mL/kg mb灌胃体积分数40%乙醇诱导血管内皮细胞损伤。榛蘑多糖低、高剂量组分别以100、400 mg/kg mb灌胃榛蘑多糖,其余组以等体积生理盐水代替,实验共进行4周。使用苏木精-伊红(hematoxylin-eosin,HE)染色观察颈动脉组织病理变化;检测血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,T-CHO)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、内皮型一氧化氮合酶、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、一氧化氮(NO)、内皮素1(endothelin 1,ET-1)、超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)水平。此外,以600μmol/mL乙醇诱导人脐静脉内皮细胞损伤模型,分析不同剂量(100、400μg/mL)榛蘑多糖对细胞活性氧(reactive oxygen species,ROS)、线粒体跨膜电位、细胞凋亡以及凋亡相关蛋白B淋巴细胞瘤2(B cell lymphoma 2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)和Caspase-3表达的影响。结果表明:榛蘑多糖减轻乙醇所致的血管内膜损伤,降低T-CHO、TG、LDL-C、iNOS、NO、ET-1和MDA水平,提高HDL-C和SOD活性;在体外条件下,榛蘑多糖降低细胞ROS水平,抑制乙醇所致的线粒体跨膜电位的下降和细胞凋亡,并提高Bcl-2/Bax,下调Cleaved caspase-3表达水平。综上,榛蘑多糖对乙醇诱导的大鼠血管内膜损伤有保护作用,机制可能与其降脂、抗氧化和抗凋亡作用有关。

黄芩苷在肺动脉高压中的研究进展

肺动脉高压是一种以肺动脉血管阻力持续升高、肺血管阻塞、血管重构、右心室肥厚、功能衰竭为特征的疾病,发病机制包括肺动脉内皮细胞功能障碍和肺动脉平滑肌细胞增殖,目前迫切需要新的治疗药物和方法。研究表明,黄芩苷对肺动脉高压的治疗有效,但具体作用机制不明。本文综述了黄芩苷药代动力学及对肺动脉高压的潜在治疗机制,主要包括抗炎反应、稳定细胞外基质、减轻氧化应激、抑制肺平滑肌细胞增殖、内皮-间质转化等,为中药治疗肺动脉高压提供依据。

组织工程角膜内皮移植研究进展

由于角膜供体材料严重短缺,穿透角膜移植术及角膜内皮移植术的临床广泛开展受到严重制约,其根本原因在于健康角膜内皮的增生能力有限。随着组织工程技术和细胞工程技术不断发展,组织工程角膜研究已取得一定进展,应用组织工程技术体外培养高密度、具备健康内皮功能的角膜内皮细胞进行移植是当前研究的热点。组织工程角膜内皮技术研发的关键在于种子细胞、载体材料和移植方式的选择。目前,国内外大量研究的种子细胞来源包括人角膜内皮细胞、干细胞、血管内皮细胞及人羊膜上皮细胞等。常见的载体材料包括羊膜、脱细胞角膜基质、后弹力层、晶状体前囊膜等。体外培养的细胞采用穿透角膜移植术、角膜内皮移植术或前房注射细胞的方式进行移植。本文从角膜内皮种子细胞来源、移植载体选择以及角膜内皮移植方法等方面就组织工程角膜内皮移植研究进展进行综述,总结目前研究面临的问题并展望其前景。

Microscopic Structure of the Sigmoido-Jugular Junction in the Third-Trimester Fetus

Context and Justification: The sigmoido-jugular junction connects two structures of different compositions and has a complex organization. The sinusoidal portion of its endothelium contains muscle cells in adults. Is this the same presentation observed in fetuses? Objective: To describe the sigmoido-jugular junction in fetuses. Materials and Methods: Over a period of seven months, a histochemical and immunohistochemical study was conducted on 30 sigmoido-jugular junctions taken from 15 fetuses aged at least 32 weeks of gestation. These fetuses were obtained following expulsion due to intrauterine death, after informed consent from the parents. Results: Three portions can be identified: sigmoid, junctional, and jugular. Histochemical preparations revealed the existence of two constant layers and a third layer present only at the jugular level. From the inside out, the layers are as follows: 1) Inner Layer (Endothelium): This layer is clearer from the junction and reveals the presence of smooth muscle cells at the sigmoid level in immunohistochemistry. 2) Outer Layer: At the sigmoid and junctional levels, this layer consists of collagen fibers and becomes median at the jugular level, where it is composed of elastic and muscular collagen fibers. 3) Third Layer: Present only at the jugular level, this layer corresponds to the adventitia. Conclusion: The architecture of the sigmoido-jugular junction in fetuses, which is identical to that in adults, excludes the metaplastic hypothesis regarding endothelial smooth muscle cells in the sigmoid portion. Instead, it favors their role in regulating encephalic venous drainage.

Differences in energy and corneal endothelium between femtosecond laser-assisted and conventional cataract surgeries：prospective,intraindividual,randomized controlled trial

AIM： To compare intraoperative phacoemulsification parameters and its effect on the corneal endothelium of eyes undergoing femtosecond laser-assisted cataract surgery（FLACS） versus conventional phacoemulsification（CP） cataract surgery.METHODS： Two hundred eyes from one hundred patients were included in a prospective, non-blinded, randomized, controlled, intraindividual clinical study. One hundred eyes underwent FLACS while their one hundred fellow eyes underwent CP. All surgeries were performed using the Victus？ femtosecond laser platform and Infinity？ Vision System phacoemulsification machine. Primary outcome measure was endothelial cell density 6 mo after surgery. Secondary outcome measures included central corneal thickness（CCT）, average cell area, standard deviation, coefficient of variation and hexagonality before surgery and 6 mo after surgery and endothelial cell density loss during this period were also evaluated. Intraoperative efficiency parameters [cumulative dissipated energy（CDE）, total intraocular surgery time, total ultrasound time, total phacoemulsification time, total torsional energy time, total aspiration time, ultrasound energy, torsional amplitude and fluid required during surgery] were also collated. RESULTS： Data from these patients was not considered for analysis. Data from 92 patients were analysed. Postoperative endothelial cell density（cells/mm2） between groups（2211.88±392.49 CP; 2246.31±403.48 FLACS） was not statistically significant（P=0.869）. Total ultrasound time, torsional energy time, CDE and fluid requirements were significantly lower the FLACS group（P〈0.05）. Other parameters did not show statistically significant difference between FLACS and CP.CONCLUSION： FLACS displays significant improvements in phacoemulsification parameters in comparison to CP. There are no significant differences in corneal endothelium measures between FLACS and CP.

Profile of biological characterizations and clinical application of corneal stem/progenitor cells

Corneal stem/progenitor cells are typical adult stem/progenitor cells.The human cornea covers the front of the eyeball,which protects the eye from the outside environment while allowing vision.The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role.Corneal stem/progenitor cells include mainly corneal epithelial stem cells,corneal endothelial cell progenitors and corneal stromal stem cells.Since the discovery of corneal epithelial stem cells(also known as limbal stem cells)in 1971,an increasing number of markers for corneal stem/progenitor cells have been proposed,but there is no consensus regarding the definitive markers for them.Therefore,the identification,isolation and cultivation of these cells remain challenging without a unified approach.In this review,we systematically introduce the profile of biological characterizations,such as anatomy,characteristics,isolation,cultivation and molecular markers,and clinical applications of the three categories of corneal stem/progenitor cells.

VEGF Deficit is Involved in Endothelium Dysfunction in Preeclampsia

This study examined the association of expression of vascular endothelial growth factor(VEGF),a promoter of angiogenesis,with endothelium dysfunction in preeclampsia.The level of VEGF protein and mRNA in the placenta and peripheral blood samples of 30 preeclampsia patients and 30 normotensive pregnant women was measured by immunohistochemistry,real-time reverse transcriptase-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA),respectively.VEGF expression in the human umbilical vein endothelial cells(HUVECs) was blocked by small interfering RNAs(siRNAs).The monolayer barrier function of HUVECs was determined by measuring the fluorescence intensity of BSA that crossed the HUVEC monolayers.The cell proliferation and cell-secreted nitric oxide(NO) level were detected by MTT method and nitrate reductase assay,respectively.The results showed that VEGF was expressed in the syncytiotrophoblasts and endothelial cells of vessels and capillaries in the placenta tissue.The serum level of VEGF in the preeclampsia patients was significantly decreased as compared with that in normal pregnant subjects,although VEGF mRNA expression in the placenta tissue of preeclampsia patients remained still high.Moreover,VEGF deficit could lead to endothelium cell dysfunction,and the administration of VEGF could protect endothelium cells from injury.It was concluded that lack of VEGF contributes to endothelium dysfunction,which may lead to the occurrence and development of preeclampsia.

Outgrowth endothelial cells form a functional cerebral barrier and restore its integrity after damage

Breakdown of blood-brain barrier,formed mainly by brain microvascular endothelial cells(BMECs),represents the major cause of mortality during early phases of ischemic strokes.Hence,discovery of novel agents that can effectively replace dead or dying endothelial cells to restore blood-brain barrier integrity is of paramount importance in stroke medicine.Although endothelial progenitor cells(EPCs)represent one such agents,their rarity in peripheral blood severely limits their adequate isolation and therapeutic use for acute ischemic stroke which necessitate their ex vivo expansion and generate early EPCs and outgrowth endothelial cells(OECs)as a result.Functional analyses of these cells,in the present study,demonstrated that only OECs endocytosed DiI-labelled acetylated low-density lipoprotein and formed tubules on matrigel,prominent endothelial cell and angiogenesis markers,respectively.Further analyses by flow cytometry demonstrated that OECs expressed specific markers for sternness(CD34),immaturity(CD133)and endothelial cells(CD31)but not for hematopoietic cells(CD45).Like BMECs,OECs established an equally tight in vitro model of human BBB with astrocytes and pericytes,suggesting their capacity to form tight junctions.Ischemic injury mimicked by concurrent deprivation of oxygen and glucose(4 hours)or deprivation of oxygen and glucose followed by reperfusion(20 hours)affected both barrier integrity and function in a similar fashion as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux,respectively.Wound scratch assays comparing the vasculoreparative capacity of cells revealed that,compared to BMECs,OECs possessed a greater proliferative and directional migratory capacity.In a triple culture model of BBB established with astrocytes,pericytes and BMEC,exogenous addition of OECs effectively repaired the damage induced on endothelial layer in serum-free conditions.Taken together,these data demonstrate that OECs may effectively home to the site of vascular injury and repair the damage to maintain(neuro)vascular homeostasis during or after a cerebral ischemic injury.

DL0805 derivatives protect the pulmonary arterial cells via the RhoA/ROCK pathway

OBJECTIVE Pulmonary artery hypertension(PAH)is a severe disease characterized by the mean pulmonary artery pressure exceeding 25 mm Hg at rest.PAH could induce right heart failure and has a very high mortality rate.At present,several kinds of drugs have been used in the treatment of PAH.However,most of these drugs aim to relax pulmonary arteries and do not inhibit the injury of vessels.In other words,the drugs available for PAH treatment do not improve the survival rate of PAH patients and cannot satisfy the needs in clinic.To discover and develop novel candidate compounds effective on the treatment of pulmonary artery injury and remodeling will be very important.Based on these background,the present study aimed to study the protective effect of two novel Rho-kinases(Rho-associated coiledcoil forming protein serine/threonine kinase,ROCK)inhibitors,DL0805 derivatives(DL0805-1and DL0805-2),on pulmonary arterial cells and further evaluate the underlying mechanisms and the possibility of DL0805 derivatives become therapeutic drugs for PAH.METHODS The primary cultured pulmonary arterial cells including human pulmonary artery endothelium cells(HPAECs)and human pulmonary artery smooth muscle cells(HPASMCs)were used in this study.HPAECs were injured under hypoxia environment(1%O2)and treated with or without DL0805 derivatives.After 48 h,the proliferation and oxidative stress were observed.CCK8 was used to detect cell viability.DCFH-DA was used as probe for reactive oxygen species(ROS)under fluorescence imaging system.HPASMCs was stimulated by growth factors including platelet-derived growth factor-BB(PDGF-BB)and Fetal Bovine Serum(FBS).The proliferation was observed in the cells treated with or without DL0805 derivatives.HPASMCs treated with or without DL0805 derivatives were further incubated with endothelin(ET-1),the proliferation and cytoskeleton remodeling of cells were detected by immunofluorescence assay.At last,Western blotting(WB)and immunofluorescence assay were employed to analysis the underlying mechanisms in the above experiments.RESULTS 10μmol·L-1DL0805-2 could inhibit the proliferation of HPAECs induced by hypoxia.Each concentration of DL0805-1 and DL0805-2attenuated the production of ROS in HPAECs.Results from WB indicated that DL0805 derivatives decreased the injury of HPAECs induced by hypoxia through the inhibition of the expression of Rho A and the activity of ROCK.On HPASMCs,DL0805 derivatives reduced the proliferation induced by PDGF-BB and FBS and inhibited cytoskeleton remodeling induced by ET-1.Immunofluorescence assay showed that DL0805 derivatives inhibited ROCK activity and down regulated the phosphorylation levels of ROCK substrates.CONCLUSION DL0805derivatives exhibited protective effect on pulmonary arterial cells including endothelium cells and smooth muscle cells.Among the above experiments,DL0805-2 showed stronger potency than DL0805-1.These two compounds might protect the cells through the inhibition of Rho A/ROCK pathway and they probably have the potential in the treatment of PAH and deserve further evaluation.

Expression of intercellular adhesion molecule 1 and interleukin 6 in the rat’s kidney after severe burn and its relation with renal injury

Objective To clarify the mechanism and provide the basis for prevention and treatme nt of the early injuries of kidney after severe burn in rats.We observed the expression of intercellular adhesion molecule 1and interleukin 6and the early p athological changes in different time.Method Early pathological changes in the kidney were observed by LM and EM.The ex pression of ICAM-1were observed by i mmunohis-tochemistry,in situ hybridization.The expression of IL-6was also obse rved.Result From 5min to 72h after burn,the early changes in the kidney included edema,hemorrhage,and congestion,injury of capillary epithelium cells.2ICAM-1and IL-6w ere higher in the kidney 30min after burn,and from 2h to 24h,they we re strongest positive,but on 72h,th ey were negative.Conclusion ICAM-1and IL-6may play important roles in mechanisms of kid ney injury,and the major target cell s may be the endothelium cells.

Effect of Captopril on Antithrombus Function of Endothelium

The experimental models of cultured porcine aortic endothelial cells(EC) in vitro were established. 6-keto-prostaglandin F1a(6-keto-PGF1a), thromboxane B2(TXB2) content, plasminogen activator(P A), plasminogen activator inhibitor(PAI) activity in cultured medium and cyclic adenosine monophosphate(cAMP) level in EC were measured with radioimmunoassay (RIA), chromogenic substrates methods, in order to assess the effect and mechanism of captopril(CP) on antithrombus function of EC. The results showed that after administration of CP, the contents of 6-keto-PGF1a and cAMP and PA activity were significantly higher, PAI activity were remarkably lower than those of control group. These effects were dose-dependent. Our finding indicated that CP might act as a prospective drug for antithrombosis through promoting anticoagulation and fibrinolysis function and increasing antithrombus action of EC.

Adhesion molecule and proinflammatory cytokine gene expression in hepatic sinusoidal endothelial cells following cecal ligation and puncture

INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].

EFFECT OF QUERCETIN ON CULTURED HUMAN VASCULAR ENDOTHELIAL CELLS

Objective To study the effects of quercetin (Que) on the release of endothelin-1 (ET-1) and prostacylin(PGI2) by normal human vascuiar endothelial cell (VEC). Methods Radioimmunoassay(RIA) was used to assess the amount of ET-1 and PGI2 produced by VEC. VEC prollferation was assessed by tetrazolium(MTT) assay. Results Que increased the normal VEC prollferation at the concentration or 5, 2o, 4o, 8o, 1oompol/L and increased the production of PG12 and inhibits the release of ET by the normal VEC at the concentratiou or 5, 2o and 8ompol/L. Que at the concentration of 5, 2o and 8omol/L had no direct effect on morphology of the normal VEC. ConcIusion Que can stimulate the proliferation of VEC and inhibit tbe reIease of ET-1 and increase the formation of PGI2. The data suggest that Que might be beneficial for the prevention and treatment of vascular endothelial injury-related cardiovascular diseases, such as atherosclerosls and thromboembolism diseases.

Migraine attack restores the response of vascular smooth muscle cells to nitric oxide but not to norepinephrine

AIM:To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.METHODS:We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography.We measuredforearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine,sodium nitroprusside or norepinephrine in 11 controls and 13patients with migraine,11 of them(M) in the interval between the migraine attacks and 4 during a headache attack(MH).Written informed consent was obtained from patients and healthy controls,and the study was approved by the Ethics Committee of the University Federico Ⅱ.RESULTS:Compared to healthy control subjects,in patients with migraine studied during the interictal period,the vasodilating effect of acetylcholine,that acts through the stimulation of endothelial cells and the release of nitric oxide,was markedly reduced,but became normal during the headache attack(P<0.05by analysis of variance).The response to nitroprusside,which directly relaxes vascular smooth muscle cells(VSMCs),was depressed in patients with migraine studied during the interictal period,but normal during the headache attack(P<0.005).During norepinephrine infusion,forearm blood flow decreased in control subjects(-40% ± 5%,P<0.001).In contrast,in patients with migraine,either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value(-3%±13% and-10.4%±15%,P>0.05).CONCLUSION:In migrainers,the impaired relaxation of VSMCs is restored during the headache attack.The vasoconstrictory response is impaired and remains unchanged during the migraine attack.

<i>ARFGEF2</i>Knockdown Enhances TNF-<i>α</i>Induced Endothelial Expression of the Cell Adhesion Molecules <i>VCAM1</i>and <i>ICAM1</i>

Sickle cell anemia (SCA) is an autosomal-recessive hemoglobinopathy with a highly variable phenotype. Multiple clinical complications are characteristic of SCA including inflammatory and oxidant damage to both small and large blood vessels, hemolysis, vasoocclusion, and premature mortality. The overall severity of SCA is affected by multiple genetic modifier loci, including ARFGEF2, a gene known to modify TNF-α receptor release from human endothelial cells. In this report, we examine the effect of siRNA mediated knockdown of ARFGEF2 inhuman pulmonary artery endothelial cells and report that TNF-α induced expression of ICAM1 and VCAM1, both important mediators of endo-thelial-leukocyte adhesion, is significantly enhanced after ARFGEF2 knockdown. Levels of ICAM-1 protein are also increased in TNF-α treated endothelial cells after ARFGEF2 knockdown;the increased ICAM-1 appears to be localized in the cytoplasm. IL-1β stimulation of endothelial cells without ARFGEF2 produced enhanced ICAM1 expression only. Additionally, ARFGEF2 knockdown distinctly altered endothelial cell morphology. Large-vessel pathology in SCA is believed to begin with endothelial activation by inflammatory cytokines and adhesion of sickle erythrocytes and leukocytes, leading to a progressive vasculopathy characterized by smooth muscle cell migration and proliferation. Understanding how variability in the function of ARFGEF2 alters the response of pulmonary vasculature to TNF-α might suggest new targets for SCA treatment.

青少年近视配戴角膜塑形镜对眼轴和角膜内皮细胞以及中央角膜厚度的影响

目的研究青少年近视配戴角膜塑形镜对眼轴和角膜内皮细胞以及中央角膜厚度的影响。方法选取2022年1~12月在本院眼视光中心经行角膜塑形术的8~16岁青少年近视80例(160只眼)为研究对象,纳入观察组,同时收集同时期90例(180只眼)配戴普通框架眼镜者为对照组。观察两组戴镜前,戴镜后3个月、6个月的眼轴情况,对两组数据进行统计分析,同时对观察组戴镜前、戴镜后3个月、6个月的角膜内皮细胞和中央角膜厚度进行比较。结果观察组配戴OK镜3个月后眼轴(24.41±0.58)mm,对照组配戴普通框架3个月后眼轴(24.50±0.69)mm,差异无统计学意义(P>0.05)。观察组配戴OK镜6个月后眼轴(24.43±0.45)mm,对照组配戴普通框架眼镜6个月后眼轴(24.59±0.58)mm,差异有统计学意义(P<0.05)。角膜内皮细胞计测定角膜内皮细胞和中央角膜厚度:配戴OK镜前为(2925.34±195.62)个/mm^(2)和(535.45±35.65)μm,戴镜后3个月为(2944.61±188.79)个/mm^(2)和(538.16±30.27)μm,戴镜后6个月为(2934.27±200.35)个/mm^(2)和(540.23±28.13)μm,三组之间差异无统计学意义(P>0.05)。结论青少年配戴普通框架镜和OK镜后眼轴长度均有增长,短期3个月内两组眼轴增加相差不大,但配戴OK镜>6个月后眼轴长度增长放慢。OK镜可以有效控制近视青少年患者眼轴增长,配戴OK镜对角膜内皮细胞和中央角膜厚度无影响。

Corneal stem cells and tissue engineering: Current advances and future perspectives

Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there aremany challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

High-density lipoprotein endocytosis in endothelial cells

AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

黄芪甲苷对氯吡格雷致大鼠胃黏膜损伤的治疗作用及机制

目的 探讨黄芪甲苷对氯吡格雷致大鼠胃黏膜损伤的治疗作用及机制。方法 将50只SD大鼠随机分为对照组、模型组及黄芪甲苷低、中、高剂量组,每组10只,分别予生理盐水1 mL/100 g、氯吡格雷15.6 mg/kg、氯吡格雷15.6 mg/kg+黄芪甲苷15、30、60 mg/kg灌胃,每日1次,干预1周后脱颈处死大鼠。用损伤指数评分评价胃黏膜损伤情况,用免疫组化SABC染色法检测胃黏膜组织中血管内皮细胞生长因子(VEGF)、磷酸化血管内皮细胞生长因子受体2(p-VEGFR2)蛋白表达。结果 与对照组比较,模型组胃黏膜损伤指数评分高,VEGF、p-VEGFR2蛋白表达低(P均<0.05);与模型组比较,各黄芪甲苷组胃黏膜损伤指数评分均低,VEGF、p-VEGFR2蛋白表达高(P均<0.05);黄芪甲苷低、中、高剂量组胃黏膜损伤指数评分逐渐降低,VEGF、p-VEGFR2蛋白表达逐渐升高(P均<0.05)。结论 黄芪甲苷可减轻氯吡格雷所致胃黏膜损伤,其作用机制可能与上调VEGF、p-VEGFR2表达有关。

内皮间质转分化在器官纤维化中的研究进展

纤维化是各组织器官在受到损伤刺激后启动的修复反应,是机体的一种自我保护机制。研究发现,内皮间质转分化(endothelial-to-mesenchymal transition,EndMT)参与心脏、肺脏、肾脏、肝脏、胰腺等多种器官纤维化的生理病理过程,已成为纤维化疾病研究的一个重点。该文将总结EndMT的调控机制及其在器官纤维化中作用,以及以EndMT为靶点的相关治疗进展,以期为器官纤维化的防治提供新的靶点。