Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer entities.Previous studies have focused on its roles as an antioxidant and in lipid peroxidation.However,the role of PNPLA8 in colorectal cancer(CRC)progression is unclear.AIM To explore the prognostic effects of PNPLA8 expression in CRC.METHODS A retrospective cohort containing 751 consecutive CRC patients was enrolled.PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores.CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile software.The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis.The over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test.RESULTS PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS.For patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant differences.Multivariate analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

Mogroside IIE,an in vivo metabolite of sweet agent,alleviates acute lung injury via Pla2g2a-EGFR inhibition

In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.

Plasma Lysophosphatidylcholine and Phospholipase A2 Activity in Chagas Disease Patients: A Comparative Analysis

Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.

In Silico Screening of Potential Inhibitors against dPLA2 from Named Chinese Herbs for Identification of Compounds with Antivenom Effects Due to Deinagkistrodon acutus Snake Bites

Phospholipase A2 (PLA2) is the key enzyme to the venom from Deinagkistrodon acutus which is one of the highly venomous snakes in China. In addition to being a catalyst for the hydrolysis of phospholipases A2 from snake venom, its well known that it possesses a broad spectrum of pharmacological activities, such as myotoxicity, neurotoxicity, cardiotoxicity, and hemolytic, anticoagulant and antiplatelet activities. However, snakebites are not efficiently treated by conventional serum therapy. Acute wounds can still cause poisoning and death. In order to find effective inhibitors of Deinagkistrodon venom acid phospholipase A2 (dPLA2), we obtained 385 compounds in 9 Chinese herbs from the TCMSP. These compounds were further performed to virtual screen using in silico tools like ADMET analysis, molecular docking and molecular dynamics (MD) simulation. After Pharmacokinetics analysis, we found 7 candidate compounds. Besides, analysis of small molecule interactions with dPLA2 confirmed that the amino acid residues HIS47 and GLY29 are key targets. Because they bind not only to the natural substrate phosphatidylcholine and compounds known for having inhibitory functions, but also for combining with potential antidote molecules in Chinese herbal medicine. This study is the first to report experience with virtual screening for possible inhibitor of dPLA2, such as the interaction spatial structure, binding energy and binding interaction analysis, these experiences not only provide reference for further experimental research, but also have a guideline for the study of drug molecular mechanism of action.

Plant Phosphatidylcholine-Hydrolyzing Phospholipases C NPC3 and NPC4 with Roles in Root Development and Brassinolide Signaling in Arabidopsis thaliana

Phosphatidylcholine-hydrolyzing phospholipase C （PC-PLC） catalyzes the hydrolysis of phosphatidylcholine （PC） to generate phosphocholine and diacylglycerol （DAG）. PC-PLC has a long tradition in animal signal transduction to generate DAG as a second messenger besides the classical phosphatidylinositol splitting phospholipase C （PI-PLC）. Based on amino acid sequence similarity to bacterial PC-PLC, six putative PC-PLC genes （NPC1 to NPC6） were identified in the Arabidopsis genome. RT-PCR analysis revealed overlapping expression pattern of NPC genes in root, stem, leaf, flower, and silique. In auxin-treated PNPc3：GUS and PNPc4：GUS seedlings, strong increase of GUS activity was visible in roots, leaves, and shoots and, to a weaker extent, in brassinolide-treated （BL） seedlings. PNPc4：GUS seedlings also responded to cytokinin with increased GUS activity in young leaves. Compared to wild-type, T-DNA insertional knockouts npc3 and npc4 showed shorter primary roots and lower lateral root density at low BL concentrations but increased lateral root densities in response to exogenous 0.05-1.0 I^M BL BL-induced expression of TCH4 and LRX2, which are involved in cell expansion, was impaired but not impaired in repression of CPD, a BL biosynthesis gene, in BL-treated npc3 and npc4. These observations suggest NPC3 and NPC4 are important in BL-mediated signaling in root growth. When treated with 0.1 I^M BL, DAG accumulation was observed in tobacco BY-2 cell cultures labeled with fluorescent PC as early as 15 min after application. We hypothesize that at least one PC-PLC is a plant signaling enzyme in BL signal transduction and, as shown earlier, in elicitor signal transduction.

R3-MYB proteins OsTCL1 and OsTCL2 modulate seed germination via dual pathways in rice

Salt and drought stress are common abiotic factors that exert a detrimental influence on seed germination,potentially leading to significantly impaired growth and production in rice.Gaining a comprehensive understanding of the molecular response of seeds to abiotic stress during the germination is of paramount importance.In the present study,we identified two R3-MYB genes in rice,namely OsTCL1 and OsTCL2,and characterized their roles in regulating seed germination under salt and drought stress.Plants with tcl1 and tcl2 mutant alleles exhibited delayed seed germination,particularly under stress conditions.The tcl1 tcl2 double mutant showed an even more pronounced reduction in germination during initial stages of germination,thereby indicating a redundant regulatory function of OsTCL1 and OsTCL2 in seed germination under abiotic stresses.Furthermore,we demonstrated that the transcript levels of several phospholipase D(PLD)genes were downregulated in the tcl1 tcl2 mutant,resulting in a decreased level of the phosphatidic acid(PA)product.Application of 1-butanol,a competitive substrate inhibitor of PLD-dependent production of PA,attenuated the stress response of the tcl1 tcl2 mutant.This suggests that OsTCL1 and OsTCL2 partially modulate seed germination through the PLD-PA signaling pathway.Moreover,there were alterations in the expression of genes involved in abscisic acid(ABA)biosynthesis,metabolism and signaling transduction in the double mutant.These changes affected the endogenous ABA level and ABA response,thereby influencing seed germination.Application of both 1-butanol and ABA synthesis inhibitor sodium tungstate(Na2WO4)nearly eliminated the differences in stress response between wild type and the tcl1 tcl2 mutant.This indicates that OsTCL1 and OsTCL2 synergistically coordinate seed germination under abiotic stresses through both the PLD-PA signaling and ABA-mediated pathways.

Functions and mechanisms of cytosolic phospholipase A_(2)in central nervous system trauma

Central nervous system(CNS)trauma,including traumatic brain injury and spinal cord injury,has a high rate of disability and mortality,and effective treatment is currently lacking.Previous studies have revealed that neural inflammation plays a vital role in CNS trauma.As the initial enzyme in neuroinflammation,cytosolic phospholipase A_(2)(cPLA2)can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids andω3-polyunsaturated fatty acid dominated by arachidonic acid,thereby inducing secondary injuries.Although there is substantial fresh knowledge pertaining to cPLA2,in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to amelio rate the clinical res ults after CNS trauma are still insufficient.The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma,highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically,neuroinflammation,lysosome membrane functions,and autophagy activity,that damage the CNS after trauma.Moreover,we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway,and we explored how those agents might be utilized as treatments to improve the results following CNS trauma.This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

磷脂酶C1基因rs2274223位点多态性与下咽癌临床病理特征及预后的相关性分析

目的 探讨磷脂酶C1(phospholipase C1,PLC1)基因rs2274223位点多态性与下咽癌临床病理特征及预后的相关性。方法 收集2016年1月~2022年12月间浙江大学医学院附属金华医院耳鼻咽喉头颈外科收治的42例下咽癌患者,所有患者均行根治手术,记录临床病理数据,并均取全血3 ml作DNA提取,Sanger法测序检测PLCE1基因rs2274223位点单核苷酸多态性,分析其与下咽癌临床病理特征及预后的相关性。结果 PLCE1基因rs2274223位点在42例下咽癌患者中有16例突变为AG,位点突变与肿瘤分化程度相关(χ^(2)=5.301,P=0.021),K-M生存分析提示rs2274223位点突变与未突变的下咽癌患者3年生存率分别为75.0%和83.1%,5年生存率分别为18.8%和31.2%,差异有统计学意义(χ^(2)=5.475,P=0.019)。结论PLCE1基因rs2274223位点突变与下咽癌低分化相关,该位点突变的下咽癌患者预后更差。

Nuclear PLD1 combined with NPM1 induces gemcitabine resistance through tumorigenic IL7R in pancreatic adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%.Of PDAC patients,15%-20%are eligible for radical surgery.Gemcitabine is an important chemotherapeutic agent for patients with PDAC;however,the efficacy of gemcitabine is limited due to resistance.Therefore,reducing gemcitabine resistance is essential for improving survival of patients with PDAC.Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC.Methods:We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment.Then,co-IP,ChIP,ChIP-seq,transcriptome sequencing,and qPCR were used to determine the specific mechanism by which phospholipase D1(PLD1)confers resistance to gemcitabine.Results:PLD1 combines with nucleophosmin 1(NPM1)and triggers NPM1 nuclear translocation,where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor(IL7R)expression.Upon interleukin 7(IL-7)binding,IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein,BCL-2,and induce gemcitabine resistance.The PLD1 inhibitor,Vu0155069,targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells.Conclusions:PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1,further promoting the downstream JAK1/STAT5/Bcl-2 pathway.Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy:A case report

BACKGROUND About 70%-80%of patients with primary membranous nephropathy(MN)have phospholipase A2 receptor(PLA2R)in renal tissue.Systemic light-chain(AL)amyloidosis is the most common type of amyloidosis.MN complicated with amyloidosis is rare.CASE SUMMARY A 48-year-old Chinese male presented with nephrotic syndrome,positive serum PLA2R antibody,and positive serum and urine IgG-lambda type M-protein,with a normal ratio of serum-free light-chain level.The patient was diagnosed with MN accompanied by AL amyloidosis.He was treated with rituximab with glucocorticoids and CyBorD regimen of chemotherapy.After 21 mo of follow-up,the patient achieved complete remission regarding nephrotic syndrome without adverse effects of chemotherapy.CONCLUSION We report a case of PLA2R-related MN complicated with primary AL amyloidosis only with renal involvement and successfully treated with rituximab,glucocorticoids and chemotherapy.

慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2和前列腺素E2及磷脂酶A2水平的变化及其临床意义

目的 观察慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2、前列腺素E2和磷脂酶A2水平变化及意义.方法 选取河北省涿州市医院2011年12月至2012年12月100例慢性阻塞性肺疾病急性加重患者,完全随机分为无呼吸衰竭组（50例）和呼吸衰竭组（50例）,另选择20例健康查体者作为健康对照组.观察3组患者血清环氧化酶2、前列腺素E2和磷脂酶A2的变化.结果 呼吸衰竭组和无呼吸衰竭组血清环氧化酶2、前列腺素E2和磷脂酶A2浓度明显高于健康对照组[（158±45）、（132±12）μg/L比（57±12）μg/L,（317±213）、（207±30）ng/L比（103±18）ng/L,（28.2±1.5）、（20.2±1.4）μg/L比（7.0±2.4）μg/L],差异均有统计学意义（均P＜0.05）.呼吸衰竭组血清环氧化酶2、前列腺素E2和磷脂酶A2浓度与无呼吸衰竭组比较,差异有统计学意义（P＜0.05）.呼吸衰竭组血清环氧化酶2、前列腺素E2水平与磷脂酶A2水平呈正相关（r分别为0.406、0.356,P＜0.05）;血清环氧化酶2水平与前列腺素E2水平呈正相关（r为0.848,P＜0.01）.结论 慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2、前列腺素E2和磷脂酶A2的浓度明显升高,血清环氧化酶2、前列腺素E2和磷脂酶A2三者之间相互关联并相互作用,共同导致呼吸衰竭的发生和发展.

阿加曲班联合阿替普酶治疗缺血性脑卒中的疗效及其对Lp-PLA_2、FIB和神经相关因子水平的影响

目的探讨阿加曲班联合阿替普酶治疗缺血性脑卒中(ischemic stroke,IS)的疗效及其对脂蛋白磷脂酶A_2(lipoprotein associated phospholipase A_2,Lp-PLA_2)、纤维蛋白原(fibrinogen,FIB)、S100钙结合蛋白A8/A9(S100A8/A9)和神经肽Y(neuropeptide Y,NPY)水平的影响。方法选取2012年9月~2015年12月期间于成都医学院附属第一医院神经内科诊治的78例IS患者为研究对象,依据治疗方法的不同将患者分为单独组(阿替普酶组)和联合组(阿加曲班+阿替普酶组),每组各39例。分别利用脑卒中量表评分、Barthel指数和长谷川简易智能量表(Hasegawa dementia scale,HDS)评估两组患者的治疗效果,比较两组患者S100A8/A9、NPY、Lp-PLA_2和FIB的变化水平。结果治疗后,两组患者的NIHSS评分均较治疗前明显降低(P<0.05),而Barthel指数和HDS量表得分值则均较治疗前显著升高(P<0.05);并且,联合组患者的NIHSS得分、Barthel指数和HDS量表评分的变化幅度均显著优于单独组(P<0.05)。治疗后,两组患者S100A8/A9、NPY、Lp-PLA_2和FIB含量均较治疗前显著降低(P<0.05),而且,联合组患者NPY和FIB水平的下降幅度明显高于单独组(P<0.05),但其余指标与单独组比较差异无统计学意义(P>0.05)。结论阿加曲班联合阿替普酶对IS患者具有显著临床疗效,可改善其自理生活能力和认知功能,促进NPY和FIB水平的恢复。

脑出血患者微创抽吸引流术前后白细胞介素-6、白细胞介素-10和磷脂酶A2水平变化及临床意义

目的:分析脑出血患者微创抽吸引流术前后白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平和磷脂酶A2(PLA2)活性变化及临床意义。方法:92例脑出血患者按照格拉斯哥昏迷指数评分分为意识清醒组(n=30)、浅昏迷组(n=36)和深昏迷组(n=26);另选体检健康人群作为对照组(n=52)。检测各组治疗前后血清IL-6、IL-10水平、PLA2活性及神经功能缺损程度评分(NIHSS),分析不同神志状态脑出血患者治疗前血清IL-6、IL-10水平与PLA2活性变化及与昏迷程度的关系;分析脑出血患者治疗前后IL-6、IL-10、PLA2水平变化及其与NIHSS评分变化的相关性。结果:治疗前不同神志状态脑出血患者血清IL-6、IL-10、PLA2水平均高于对照组(P<0.01),且随昏迷程度加重而逐渐升高,血清IL-6、IL-10、PLA2水平均与昏迷程度呈正相关(rIL-6=0.583、rIL-10=0.608、rPLA2=0.552,P<0.05)。治疗后,脑出血患者血清IL-6、IL-10、PLA2水平较治疗前明显均降低,NIHSS评分也显著降低(P<0.01),血清IL-6、IL-10、PLA2与NIHSS评分亦呈正相关(rIL-6=0.617、rIL-10=0.569、rPLA2=0.655,P<0.05)。结论:IL-6、IL-10、PLA2等水平变化可反映脑出血病情,微创抽吸引流术可有效减轻脑出血患者神经功能缺损程度。

严重烧伤脓毒症患者血清TNF-α、IL-6、IL-10、PLA2的变化及器官功能损害状况分析

目的研究严重烧伤脓毒症患者血清肿瘤坏死因子-α(TNF-α)、IL-6、IL-10、血清磷脂酶A2(PLA2)的变化及器官功能损害状况。方法该院自2010年3月至2011年3月共收治重度烧伤患者57例,33例发生脓毒血症,其中19例并发多器官功障碍综合征(MODS)。将其按照并发症状况分为脓毒血症组(S组)、脓毒血并发MODS组(M组)及阴性组(N组),对比3组患者的基本情况,IL-10、IL-6、TNF-α、PLA2等炎性相关介质浓度差异及变化趋势,器官功能障碍发病状况等。结果 S组和M组患者的PLA2、TNF-α、IL-6值明显高于N组,且治疗后无明显下降;3组患者血清IL-10变化趋势差异无统计学意义(P>0.05)。并发脓毒血症或MODS烧伤患者的烧伤面积较大、深度较深,器官衰竭及病死率显著高于一般烧伤患者,并以呼吸循环功能衰竭最为常见。结论严重烧伤患者的血浆PLA2、TNF-α、IL-6水平与烧伤程度呈正相关,其活性持续维持在高水平可能与患者发生脓毒血症及MODS密切相关,影响患者愈后。

糖尿病冠状动脉粥样硬化性心脏病患者测定血清脂蛋白相关磷脂酶A2和血脂水平的临床价值

目的：探讨糖尿病冠状动脉粥样硬化性心脏病（简称糖尿病冠心病）患者血清脂蛋白相关磷脂酶A2（Lp-PLA2）和血脂（TG、HDL-C、LDL-C、Lp（a）、ApoA1、ApoB和ApoB/ApoA1比值）水平的临床价值。方法采用酶联免疫分析、生化法和免疫比浊分析测定157例糖尿病冠心病患者血清Lp-PLA2和血脂水平，并与60名健康对照组进行比较性分析。受试者工作曲线（ROC曲线）分析血清Lp-PLA2、TG、HDL-C、LDL-C、Lp（a）、ApoA1、ApoB水平，并进行预测冠状动脉粥样硬化性心血管疾病（CVD）的性能评估。结果糖尿病冠心病患者血清Lp-PLA2、TG、LDL-C、Lp（a）、ApoB和ApoB/ApoA1比值水平明显增高，而血清HLD-C、ApoA1水平稍降低。ROC曲线分析表明：血清Lp-PLA2、LDL-C、ApoA1和ApoB水平具有预测冠状动脉硬化性CVD性能的价值，并以血清Lp-PLA2为最佳。结论糖尿病冠心病的特点是血糖和血脂代谢紊乱，胰岛素抵抗和高尿酸血症，血清Lp-PLA2、LDL-C、ApoA1、ApoB和ApoB/ApoA1比值测定具有早期诊断的临床价值，血清Lp-PLA2、LDL-C、ApoA1和ApoB水平是预测冠心病心血管事件的有价值指标。

力学敏感TRPC通道介导心肌细胞肥大的力学门控新机制初探

研究背景力学门控性离子通道（mechanogated ion channels）,又称为力学敏感性离子通道（mechanosensitive ion channels,MSIC）,是心肌细胞的力学感受器之一。MSIC在心脏受到力学超负荷后电生理改变过程中起主要作用,可能是心肌细胞肥大过程中,力学负荷与蛋白质合成之间信号传导的一条重要通路。瞬时感受器电位（Transient receptor potential,TRP）离子通道C亚族（TRPC）蛋白TRPC1、C6对于心肌细胞适应生物力学刺激很重要,其表达上调会导致病理性心肌肥大及心衰[1-3]。TRPC通道不仅可被G蛋白耦联受体下游的磷脂酶C（phospholipase C,PLC）、二脂酰甘油（diacylglycerol,DAG）等信号分子继发激活,TRPC1、C6等可能还是力学敏感的离子通道,

Phospholipase A_2 changes and its significance on brain tissue of rat in severe acute pancreatitis

Objective To survey changes and the significance of phospholipase A_2(PLA_2) on brain tissue of SD rat in acute pancreatitis.Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct,rat model of severe acute pancreatitis(SAP) was made,and it included four groups: the control group,the sham-operation group, the SAP group and the PLA_2 inhibitor-treated group of SAP.Serum amylases,PLA_2 and PLA_2 in brain tissue were measured and the brain tissue changes were observed.Results There were no significant difference in serum amylases, PLA_2 and PLA_2 in brain tissue between the sham-operation and the control groups;the levels of serum amylases,PLA_2 and PLA_2 in brain tissue in the SAP group were higher than those in the control.In the SAP group expansion and hemorrhage of meninges,intracephalic arteriolar hyperemia,in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed,significant differences were found between two groups.Compared with the SAP group,the level of serum amylase,PLA_2 and PLA_2 in brain tissue were reduced significantly in the treatment group of SAP.Pathological damages in the treatment group were significantly reduced when compared with the SAP group.Conclusion PLA_2 might play an important role in brain tissue damages in severe acute pancreatitis.

表观健康人群血清脂蛋白相关磷脂酶A_2参考区间的建立

目的建立上海地区表观健康人群血清脂蛋白相关磷脂酶A_2(Lp-PLA_2)的参考区间。方法检测800名健康体检者(男、女性各400名)血清Lp-PLA_2活性,根据美国临床实验室标准化协会(CLSI)C28-A3文件的相关要求,以百分位数法确定Lp-PLA_2的95%参考区间[第2.5百分位数(P2.5)~第97.5百分位数(P97.5),可信区间为90%]。结果表观健康人群血清Lp-PLA_2活性呈正态分布。男性Lp-PLA_2活性为(479±126)U/L,女性为(433±118)U/L,二者间差异有统计学意义(t=5.311,P<0.01)。男性血清LpPLA_2活性保持恒定,女性血清Lp-PLA_2活性随年龄的增加而呈升高趋势,各年龄段Lp-PLA_2活性比较差异有统计学意义(F=2.017,P<0.05)。进一步分析显示<50岁的各年龄组之间和≥50岁的各年龄组之间Lp-PLA_2活性差异均无统计学意义(P>0.05),因此将女性各年龄组合并为18~49岁组和50~89岁组。由此得出上海地区表观健康人群血清Lp-PLA_2的参考区间男性为219~694 U/L,女性18~49岁为204~651 U/L、50~89岁为217~686 U/L。结论初步建立了上海地区表观健康人群血清Lp-PLA_2的参考区间,为临床应用Lp-PLA_2作为心血管疾病风险评估指标提供依据。