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Identification of TRPM7 channels in human intestinal interstitial cells of Cajal 被引量:3
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作者 Byung Joo Kim Kyu Joo Park +6 位作者 Hyung Woo Kim Seok Choi Jae Yeoul Jun In Youb Chang Ju-Hong Jeon Insuk So Seon Jeong Kim 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第46期5799-5804,共6页
AIM: To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS: Conventional microel... AIM: To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS: Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat (ICCs). RESULTS: The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB (2-aminoethoxydiphenyl borate) and La3+, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION: These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves. 展开更多
关键词 ELECTROPHYSIOLOGY Interstitial cells of Cajal TRPM cation channels Transient receptor potential melastatin-type 7 protein HUMAN Gastrointestinal tract
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MLKL forms cation channels 被引量:1
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作者 XIA Bing-qing FANG Sui +4 位作者 CHEN Xue-qin HU Hong CHEN Pei-yuan WANG Hua-yi GAO Zhao-bing 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1047-1047,共1页
The mixed lineage kinase domain-like(MLKL)protein is a key factor in tumor necrosis factor-induced necroptosis.Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption.However,... The mixed lineage kinase domain-like(MLKL)protein is a key factor in tumor necrosis factor-induced necroptosis.Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption.However,our knowledge of how MLKL functions on membrane remains very limited.Here we demonstrate that MLKL forms cation channels that are permeable preferential y to Mg2+rather than Ca2+in the presence of Na+and K+.Moreover,the N-terminal domain containing six helices(H1-H6)is sufficient to form channels.Using the substituted cysteine accessibility method,we further determine that helix H1,H2,H3,H5 and H6 are transmembrane segments,while H4 is located in the cytoplasm.Finally,MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity.The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels. 展开更多
关键词 cation channels mixed lineage kinase domain-like
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Involvement of hyperpolarization-activated,cyclic nucleotide-gated cation channels in dorsal root ganglion in neuropathic pain 被引量:9
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作者 WAN You 《生理学报》 CAS CSCD 北大核心 2008年第5期579-580,共2页
Dorsal root ganglion(DRG)neurons have peripheral terminals in skin,muscle,and other peripheral tissues,andcentral
关键词 环核苷酸 神经节 神经性疼痛 临床分析
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MLKL forms cation channels
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作者 Bing-qing XIA Sui FANG +4 位作者 Xue-qin CHEN Hong HU Pei-yuan CHEN Hua-yi WANG Zhao-bing GAO 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期1017-1017,共1页
OBJECTIVE To investigate how MLKL functions on the membrane and explore its electrophysiological characters and structure.METHODS The full-length human MLKL were expressed in SF21 cells and purified using glutathione-... OBJECTIVE To investigate how MLKL functions on the membrane and explore its electrophysiological characters and structure.METHODS The full-length human MLKL were expressed in SF21 cells and purified using glutathione-sepharose affinity chromatography.The currents of purified MLKL proteins were recorded in avoltage-clamp mode using a Warner BC-535 bilayer clamp amplifier.The currents were digitized using p CLAMP 10.2 software.HEK293 cells were cultured and transfected with MLKL plasmid.Cell viability was examined using the Cell Titer-Glo Luminescent Cell Viability Assay kit.RESULT MLKL forms cation channels that are permeable preferentially to Mg2+rather than Ca2+in the presence of Na+and K+.Moreover,each MLKL monomer contains five transmembrane helices:H1,H2,H3,H5 and H6 of the N-terminal domain which is sufficient to form channels.Finally,MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. 展开更多
关键词 MLKL magnesium channel bilayer lipid membrane cation channel NECROPTOSIS
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Distribution profiles of transient receptor potential melastatin-related and vanilloid-related channels in prostatic tissue in rat 被引量:3
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作者 Huai-Peng Wang Xiao-Yong Pu Xing-Huan Wang 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第5期634-640,共7页
Aim: To investigate the expression and distribution of the members of the transient receptor potential (TRP) channel members of TRP melastatin (TRPM) and TRP vanilloid (TRPV) subfamilies in rat prostatic tissue... Aim: To investigate the expression and distribution of the members of the transient receptor potential (TRP) channel members of TRP melastatin (TRPM) and TRP vanilloid (TRPV) subfamilies in rat prostatic tissue. Methods: Prostate tissue was obtained from male Sprague-Dawley rats. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time polymerase chain reaction (PCR) were used to check the expression of all TRPM and TRPV channel members with specific primers. Immunohistochemistry staining for TRPM8 and TRPV1 were also performed in rat tissues. Results: TRPM2, TRPM3, TRPM4, TRPM6, TRPM7, TRPMS, TRPV2 and TRPV4 mRNA were detected in all rat prostatic tissues. Very weak signals for TRPM1, TRPVI and TRPV3 were also detected. The mRNA of TRPM5, TRPV5 and TRPV6 were not detected in all RT-PCR experiments. Quantitative real-time RT-PCR showed that TRPM2, TRPM3, TRPM4, TRPMS, TRPV2 and TRPV4 were the most abundantly expressed TRPM and TRPV subtypes, respectively. Fluorescence immunohistochemistry indicated that TRPM8 and TRPV 1 are highly expressed in both epithelial and smooth muscle cells. Conclusion: Our results demonstrate that mRNA or protein for TRPM1, TRPM2, TRPM3, TRPM4, TRPM6, TRPM7, TRPMS, TRPV1, TRPV2, TRPV3 and TRPV4 exist in rat prostatic tissue. The data presented here assists in elucidating the physiological function of TRPM and TRPV channels. 展开更多
关键词 transient receptor potential channels PROSTATE cation channels
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Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Cation Channel 4 Involved in Microwave Induced Pacemaker Cell Injuries 被引量:3
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作者 LIU Yan Qing ZHAO Li +6 位作者 GAO Ya Bing DONG Ji WANG Hui YAO Bin Wei ZHOU Hong Mei WANG Shui Ming PENG Rui Yun 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2015年第11期823-828,共6页
To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower sp... To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2+ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 (HCN4) was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node (SAN) of the rats, 展开更多
关键词 HCN In node Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated cation channel 4 Involved in Microwave Induced Pacemaker Cell Injuries SAN ISH Figure ACH AR
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Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury 被引量:3
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作者 Fei Ren Hong Zhang +3 位作者 Chao Qi Mei-ling Gao Hong Wang Xia-qing Li 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第8期1324-1331,共8页
The transient receptor potential cation channel subfamily V member 1(TRPV1) provides the sensation of pain(nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe... The transient receptor potential cation channel subfamily V member 1(TRPV1) provides the sensation of pain(nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517(300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve. 展开更多
关键词 nerve regeneration peripheral nerve regeneration transient receptor potential cation channel subfamily V member 1 capsaicin receptor vanilloid receptor TRPV1 antagonist nociceptor nerve crush injury Wallerian degeneration axon NSFC grant neurites neural regeneration
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Influence of Associated Cations on the Transport and Adsorption of Chloride Ions in the Nano-channel of Calcium Aluminosilicate Hydrate Gel:A Molecular Dynamics Study
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作者 YANG Jun ZHANG Gaozhan +2 位作者 DING Qingjun WANG Aiguo HOU Dongshuai 《Journal of Wuhan University of Technology(Materials Science)》 SCIE EI CAS 2022年第5期963-976,共14页
Molecular dynamics simulation was utilized to investigate the transport and adsorption of chloride in the nanopore of calcium aluminosilicate hydrate(C-A-S-H)with associated cation types of Ca,Mg,Na and K.The local io... Molecular dynamics simulation was utilized to investigate the transport and adsorption of chloride in the nanopore of calcium aluminosilicate hydrate(C-A-S-H)with associated cation types of Ca,Mg,Na and K.The local ionic structure,atomic dynamics and bond stability were analyzed to elucidate the interaction between cations and chloride ions.The results show that interfacial chloride is absorbed through the ion pairing formation in the vicinity of C-A-S-H substrate.Interfacial cations can simultaneously interact aluminosilicate chains,water molecules and Cl^(-)ions,which restrict the motion of interfacial Cl^(-)ions.Pore solution chloride can be immobilized through the solvation effect of cations.Cations along with their hydration shell can connect to neighboring Cl^(-)ions to decrease their mobility.Owing to the varied ionic chemistry,cations show different interaction strength with neighboring water molecules and anions,which determines the chloride transport behavior in the nanopore of C-A-S-H.The chloride immobilization capacity of C-A-S-H nanopore with different associated cations is listed in following order:Mg^(2+)Ca^(2+)<Na^(+)≈K^(+),which agrees reasonably with previous experiments. 展开更多
关键词 calcium aluminosilicate hydrate nanometer channel confinement chloride immobilization associated cations ionic structure
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Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity
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作者 Unal Atas Nuray Erin +2 位作者 Gokhan Tazegul Gulsum Ozlem Elpek Bülent Yıldırım 《World Journal of Clinical Cases》 SCIE 2022年第1期79-90,共12页
BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaici... BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients. 展开更多
关键词 CAPSAICIN Transient receptor potential vanilloid 1 IMMUNOHISTOCHEMISTRY Morbid obesity OBESITY Transient receptor potential channels Transient receptor potential vanilloid cation channels
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A Fast Algorithm of Scalar Multiplication Based on Side-Channel Atomicity
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作者 郝玉洁 殷石 《China Communications》 SCIE CSCD 2011年第2期134-139,共6页
Simple power analysis is the most devastating attack on the security of elliptic curve scalar multiplication and can probably retrieve the secret key. In this paper,we analyze the formulas of point doubling and additi... Simple power analysis is the most devastating attack on the security of elliptic curve scalar multiplication and can probably retrieve the secret key. In this paper,we analyze the formulas of point doubling and addition on Jacobi-quartic Curve in projective coordination. In addition,a fast and secure side-channel atomic scalar multiplication algorithm is proposed using the side-channel atomic block. Compared with the previous methods,the new algorithm is more efficient. For 192 bits scalar using NAF recoding,the efficiency of the new algorithm is increased by about 6.7%~23% if S/M=0.8 or 12.7%~33.2% if S/M=0.6. 展开更多
关键词 jacobi-quartic curve scalar multipli-cation simple power analysis side-channel atomicity
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瞬时感受器电位离子通道香草素受体亚家族Ⅳ在帕金森病细胞模型中介导PC12细胞炎症反应的机制
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作者 吴基林 李慧娴 +4 位作者 李义红 邱昢 李云霞 刘娜 李丽萍 《安徽医药》 CAS 2024年第11期2165-2168,I0005,共5页
目的探讨瞬时感受器电位离子通道香草素受体亚家族Ⅳ(TRPV4)在帕金森病(PD)细胞模型中介导PC12细胞炎症反应的机制。方法2023年6―8月,用1-甲基-4-苯基吡啶离子(MPP^(+))建立PD细胞模型,用TRPV4特异性抑制剂HC067047抑制TRPV4。将培养的... 目的探讨瞬时感受器电位离子通道香草素受体亚家族Ⅳ(TRPV4)在帕金森病(PD)细胞模型中介导PC12细胞炎症反应的机制。方法2023年6―8月,用1-甲基-4-苯基吡啶离子(MPP^(+))建立PD细胞模型,用TRPV4特异性抑制剂HC067047抑制TRPV4。将培养的PC12细胞采用随机数字表法分为四组:对照组、HC067047组、MPP^(+)组、HC067047+MPP^(+)组。细胞毒性检测试剂盒(CCK-8)检测各组细胞的增殖活力。蛋白印迹法和酶联免疫吸附测定(ELISA)检测各组细胞TRPV4和炎症因子白细胞介素-18(IL-18)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的水平变化。结果与对照组1.00±0.08相比,MPP^(+)组TRPV4的表达量2.14±0.20明显升高(P<0.001)。与对照组1.00±0.01相比,MPP^(+)组的PC12细胞活力0.65±0.08明显降低(P<0.01),而HC067047能明显回复MPP^(+)引起的细胞活力0.83±0.07降低(P<0.01)。与对照组相比,MPP^(+)组的IL-181.96±0.27和IL-61.92±0.18、IL-1β(874.61±108.09)ng/L和TNF-α(791.28±106.88)ng/L明显升高(P<0.001),HC067047能明显抑制MPP^(+)引起的IL-181.45±0.11和IL-61.58±0.22、IL-1β(626.28±84.53)ng/L和TNF-α(592.94±86.9)4 ng/L明显升高(P<0.01或P<0.05)。结论TRPV4参与了MPP^(+)诱导的PD细胞模型的炎症反应,抑制TRPV4有抗炎作用。 展开更多
关键词 TRPV阳离子通道 香草素受体亚家族Ⅳ 帕金森病 炎症反应 细胞模型
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线粒体氧化应激及m6A表观遗传调控TRPC6钙通道在肾病综合征发病中的作用研究
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作者 姜丽娜 孔玮晶 丁瑛雪 《临床和实验医学杂志》 2024年第8期785-789,共5页
目的 初步探讨N6-甲基腺嘌呤(m6A)表观遗传修饰瞬时受体电位阳离子通道6(TRPC6)通道失调在肾病综合征发病中的作用及潜在机理。方法 按照随机数字表法将小鼠足细胞分为4组:对照组、叔丁基对苯二酚(TBHQ)组、嘌呤霉素氨基核苷(PAN)处理组... 目的 初步探讨N6-甲基腺嘌呤(m6A)表观遗传修饰瞬时受体电位阳离子通道6(TRPC6)通道失调在肾病综合征发病中的作用及潜在机理。方法 按照随机数字表法将小鼠足细胞分为4组:对照组、叔丁基对苯二酚(TBHQ)组、嘌呤霉素氨基核苷(PAN)处理组、TBHQ+PAN处理组。对照组为正常完全培养液,TBHQ组培养液中加入10 nmol/L TBHQ,PAN处理组培养液中加入PAN 50μg/mL,TBHQ+PAN处理组培养液中加入10 nmol/L TBHQ以及PAN 50μg/mL,刺激24 h收集细胞。应用膜片钳证实PAN损伤诱导TRPC6通道激活机理及1,4,5-肌醇三磷酸(IP3)受体拮抗剂TBHQ对电流的影响,检测对照组、PAN处理组、TBHQ组和TBHQ+PAN处理组细胞TRPC6通道电流变化。通过葡萄糖氧化酶(GO)建立足细胞氧化应激模型。另外按照随机数字表法将足细胞分为4组:空白对照组、GO组、姜黄素组、姜黄素+GO组。GO组给予GO 3.5 kU/L,姜黄素组给予Nrf2激动剂(姜黄素)40μmol/L,姜黄素+GO组给予姜黄素40μmol/L和GO 3.5 kU/L处理,给药处理8~12 h后收集细胞。检测各组Nrf2和特异性调控蛋白NAD(P)H:醌氧化还原酶1(NQO-1)、TRPC6及Transgelin蛋白和线粒体调控蛋白表达变化。通过SRAMP对TRPC6通道m6A位点进行精准预测,对PAN诱导足细胞损伤模型公共数据库GSE124622进行2次生物信息学分析。结果 对照组与TBHQ组电流比较,差异无统计学意义(P>0.05);与对照组比较,PAN处理组电流升高,而TBHQ+PAN组电流减小,差异均有统计学意义(P<0.05)。与空白对照组比较,GO组Nrf2、NQO-1、TRPC6及Transgelin蛋白表达均升高,差异均有统计学意义(P<0.01);与GO组比较,姜黄素+GO组Nrf2、NQO-1、TRPC6及Transgelin蛋白表达均降低,差异均有统计学意义(P<0.05)。与空白对照组比较,GO组线粒体调控蛋白Mfn2、Opa1蛋白表达均降低,Drp1蛋白表达升高,差异均有统计学意义(P<0.05);与GO组比较,姜黄素+GO组粒体调控蛋白Mfn2、Opa1蛋白表达升高,Drp1蛋白表达降低,差异均有统计学意义(P<0.05);空白对照组与姜黄素组TRPC6/Transgelin及线粒体调控蛋白表达比较,差异均无统计学意义(P>0.05)。TRPC6通道序列存在多个m6A修饰位点,均具有被甲基转移酶(METTL)3、METTL14、肾母细胞肿瘤1相关蛋白(WTAP)和去甲基化酶ALKB同源蛋白(ALKBH)、m6A去甲基化酶(FTO)调控的潜在可能。对12个m6A调节基因进行表达分析,发现m6A调节基因的表达在PAN诱导足细胞损伤中发生显著差异。结论 TRPC6介导钙离子内流可被氧化应激激活参与足细胞损伤,激活Nrf2可以减少钙过负荷所致线粒体损伤而保护足细胞。TRPC6序列中存在多个高m6A修饰靶点,肾病综合征发病机理可能通过m6A修饰足细胞TRPC6离子通道,m6A相关调控基因在肾病足细胞损伤中发生明显变化。 展开更多
关键词 肾病综合征 嘌呤霉素 氨基核苷 瞬时受体电位阳离子通道6 线粒体功能异常 N6-甲基腺嘌呤 m6A转移酶样3抑制剂
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桔梗素D通过下调成纤维细胞TRPC6表达改善小鼠肺纤维化 被引量:2
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作者 梁梓琛 余常辉 +5 位作者 梁世秀 周梓聪 周子丽 孟晓静 邹飞 蔡绍曦 《南方医科大学学报》 CAS CSCD 北大核心 2024年第1期60-69,共10页
目的探究桔梗素D(PD)对肺纤维化的影响及其机制。方法博来霉素(BLM)气道内滴入构建C57BL/6J小鼠肺纤维化模型,再予PD(10 mg/kg)灌胃,28 d后处死小鼠。分组如下:对照组(control)、BLM(10 mg/kg)模型组、BLM(10 mg/kg)+PD(10 mg/kg)组。... 目的探究桔梗素D(PD)对肺纤维化的影响及其机制。方法博来霉素(BLM)气道内滴入构建C57BL/6J小鼠肺纤维化模型,再予PD(10 mg/kg)灌胃,28 d后处死小鼠。分组如下:对照组(control)、BLM(10 mg/kg)模型组、BLM(10 mg/kg)+PD(10 mg/kg)组。肺组织石蜡切片HE染色、免疫组化和天狼星红染色评估小鼠肺组织纤维化程度和瞬时受体电位离子通道亚族C成员6(TRPC6)的表达与分布。Westernblot检测肺组织α-平滑肌肌动蛋白(α-SMA)的表达水平。小鼠原代肺成纤维细胞体外培养,分别用PD、TRPC6抑制剂醋酸落叶松酯(LA)预处理后加入转化生长因子-β1(TGF-β1)刺激细胞,根据加入的TGF-β1和PD浓度不同分组如下:control组、TGF-β1(10 ng/mL)组、PD(2.5μmol/L)+TGF-β1组、PD(5μmol/L)+TGF-β1组和PD(10μmol/L)+TGF-β1组,LA处理分组如下:control组、TGF-β1(10 ng/mL)组和LA(10μmol/L)+TGF-β1组,测定细胞存活率、collagenⅠ、α-SMA和TRPC6的表达水平、活性氧(ROS)生成水平、线粒体膜电位、细胞增殖能力等指标。利用网络药理学方法结合文献分析PD作用于肺纤维化可能通过的机制。结果PD可明显减轻BLM诱导小鼠模型的肺部纤维化程度、减少α-SMA表达(P<0.05)。CCK-8结果显示PD、TGF-β1和LA的最适宜刺激浓度分别是10μmol/L、10 ng/mL和10μmol/L;5-乙炔基-2'-脱氧尿苷(EdU)染色结果显示PD能够有效抑制肺成纤维细胞增殖;2,7-二氯荧光素二乙酸酯(DCFH-DA)染色显示PD能有效减少TGF-β1诱导的细胞ROS生成(P<0.0001);线粒体膜电位检测(Jc-1染色)结果显示PD能有效缓解TGF-β1诱导的细胞线粒体膜电位下降(P<0.001);蛋白电泳结果显示PD能显著抑制TGF-β1诱导的α-SMA和collagenⅠ的表达(P<0.05)。网络药理学结合文献分析发现PD可能通过TRPC6作用于肺纤维化。免疫组织化学结果显示PD明显减轻了BLM诱导的肺组织TRPC6表达。蛋白电泳结果显示PD可明显抑制TGF-β1诱导的TRPC6表达(P<0.05);使用LA可明显抑制细胞TRPC6、α-SMA、collagenⅠ的表达(P<0.05)。结论PD可降低小鼠肺纤维化,其机制可能与下调TRPC6并减少ROS产生有关。 展开更多
关键词 肺纤维化 桔梗素D 瞬时受体电位离子通道亚族C成员6 活性氧
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TRPV3在皮肤病发生及治疗中的研究进展
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作者 魏明镜 陈文琦 《中国麻风皮肤病杂志》 2024年第1期66-70,共5页
瞬时受体电位离子通道香草素3(transient receptor potential vanilloid 3,TRPV3)是一种非选择性阳离子通道蛋白,在皮肤角质形成细胞中表达最为丰富,参与角质形成细胞增殖、皮肤屏障形成、感觉传导、毛发生长等生理过程,对维持皮肤稳态... 瞬时受体电位离子通道香草素3(transient receptor potential vanilloid 3,TRPV3)是一种非选择性阳离子通道蛋白,在皮肤角质形成细胞中表达最为丰富,参与角质形成细胞增殖、皮肤屏障形成、感觉传导、毛发生长等生理过程,对维持皮肤稳态有着重要作用。研究发现TRPV3在特应性皮炎、Olmsted综合征、银屑病等皮肤病的发生发展中起重要作用。本文将对TRPV3在上述皮肤病的发病机制中产生的作用及其未来的临床应用进行综述。 展开更多
关键词 特应性皮炎 TRPV3 阳离子通道 OLMSTED综合征
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冰片通过TRPM8减轻小鼠心肌梗死后炎症反应并抑制心脏重构 被引量:2
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作者 何滢蓉 胡陶 +4 位作者 王武帅 杨曦 段清华 杜萱 王强 《中国病理生理杂志》 CAS CSCD 北大核心 2024年第3期456-464,共9页
目的:研究冰片(borneol)对小鼠心肌梗死(myocardial infarction,MI)后炎症反应和心脏重构的作用及可能机制。方法:8周龄野生型(wild-type,WT)C57BL/6小鼠和瞬时受体电位阳离子通道M亚家族成员8(transient receptor potential cation cha... 目的:研究冰片(borneol)对小鼠心肌梗死(myocardial infarction,MI)后炎症反应和心脏重构的作用及可能机制。方法:8周龄野生型(wild-type,WT)C57BL/6小鼠和瞬时受体电位阳离子通道M亚家族成员8(transient receptor potential cation channel subfamily M member 8,TRPM8)基因敲除(TRPM8 gene knockout,TRPM8−/−)小鼠随机分为假手术组和MI组,再分别用生理盐水(对照组)或冰片(冰片组)灌胃。绘制小鼠MI后生存曲线,28 d后超声心动图检测心脏功能,多导生理记录仪测量血流动力学参数,病理染色观察MI面积、心肌肥大和间质纤维化,并检测梗死交界区心肌中炎症反应情况。结果:在WT小鼠中,梗死交界区心肌组织中TRPM8表达显著增加(P<0.05),冰片对心脏中TRPM8表达无影响(P>0.05),但可提高小鼠生存率,缩小MI面积,抑制MI后心脏重构,改善心脏功能(P<0.05或P<0.01);在TRPM8−/−小鼠中,冰片对小鼠生存率、MI面积、心肌肥大、心肌纤维化和心脏功能未见明显影响(P>0.05)。在WT小鼠中,冰片可减少中性粒细胞和巨噬细胞的浸润(P<0.01),抑制炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、IL-6和单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)过度表达(P<0.05或P<0.01);而在TRPM8−/−小鼠中,冰片对炎症细胞数量和炎症因子表达未见明显影响(P>0.05)。结论:TRPM8可能是冰片在心脏的作用靶点;冰片可能通过TRPM8减轻MI后炎症反应和抑制心脏重构,改善小鼠MI后的心脏功能。 展开更多
关键词 心肌梗死 心脏重构 冰片 瞬时受体电位阳离子通道M亚家族成员8 炎症
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TRPC3对OIR小鼠视网膜和人视网膜血管内皮细胞生物学行为的调控作用
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作者 张越 刘晓静 +10 位作者 甄宇涵 姚瑶 邵斌 徐嫚鸿 王艳辉 刘志强 王伟 毛爱玲 张宝月 张铭连 陈志敏 《中华实验眼科杂志》 CAS CSCD 北大核心 2024年第4期331-338,共8页
目的探讨瞬时受体电位阳离子通道亚家族C成员3(TRPC3)对氧诱导视网膜病变(OIR)小鼠视网膜和人视网膜血管内皮细胞(HREC)生物学行为的调控作用。方法选取健康SPF级7日龄C57BL/6小鼠32只,采用随机数字表法分为对照组和OIR组,每组16只,其... 目的探讨瞬时受体电位阳离子通道亚家族C成员3(TRPC3)对氧诱导视网膜病变(OIR)小鼠视网膜和人视网膜血管内皮细胞(HREC)生物学行为的调控作用。方法选取健康SPF级7日龄C57BL/6小鼠32只,采用随机数字表法分为对照组和OIR组,每组16只,其中对照组不做特殊处理,OIR组小鼠诱导OIR模型。出生后第17天(PN17)采用视网膜铺片免疫荧光染色验证模型构建是否成功。将体外培养HREC分为正常对照组、转染试剂组和si-TRPC3组,其中正常对照组不做特殊处理,转染试剂组和si-TRPC3组分别采用转染试剂和转染试剂+si-TRPC3转染。采用实时荧光定量PCR法检测TRPC3 mRNA相对表达量;采用Western blot法检测TRPC3、转录因子NF-E2相关因子(Nrf2)和超氧化物歧化酶(SOD)蛋白相对表达量。另将HREC分为正常对照组、血管内皮生长因子(VEGF)组、si-TRPC3组和Pyr3(TRPC3通道抑制剂)组,分别用完全培养基、含有20 ng/ml VEGF重组蛋白的培养基、含有20 ng/ml VEGF重组蛋白的培养基(si-TRPC3转染72 h)和含有20 ng/ml VEGF重组蛋白+1μmol/L Pyr3的培养基培养48 h,采用细胞计数试剂盒8(CCK-8)检测HREC增生能力;分别采用细胞划痕实验和Transwell实验检测细胞横向和纵向迁移能力。结果PN17时OIR组小鼠视网膜出现病理性新生血管团簇强荧光染色。OIR组小鼠视网膜TRPC3 mRNA和蛋白相对表达量分别为2.057±0.244和1.517±0.290,明显高于对照组的0.983±0.033和0.874±0.052,差异均有统计学意义(t=6.165、3.094,均P<0.05)。si-TRPC3组TRPC3 mRNA和蛋白相对表达量明显低于正常对照组和转染试剂组,Nrf2和SOD蛋白相对表达量明显高于正常对照组和转染试剂组,差异均有统计学意义(均P<0.05)。CCK-8实验结果显示,VEGF组细胞吸光度(A)值明显高于正常对照组,si-TRPC3组和Pyr3组细胞A值明显低于VEGF组,差异均有统计学意义(均P<0.05)。细胞划痕实验结果显示,VEGF组细胞横向迁移率高于正常对照组,si-TRPC3组和Pyr3组细胞横向迁移率低于VEGF组,差异均有统计学意义(均P<0.05)。Transwell实验结果显示,VEGF组染色细胞数明显多于正常对照组,si-TRPC3组和Pyr3组染色细胞数明显少于VEGF组,差异均有统计学意义(均P<0.05)。结论OIR模型小鼠视网膜中TRPC3表达水平升高,下调TRPC3可抑制HREC增生和迁移能力,其机制与Nrf2氧化应激通路激活有关。 展开更多
关键词 视网膜疾病 氧化应激 瞬时受体电位阳离子通道亚家族C成员3 人视网膜血管内皮细胞
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TRPC6对糖尿病肾病小鼠肾小管间质炎症的影响及其机制
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作者 刘丛聪 张行健 +3 位作者 丁琳 张瑶 张栋杰 马瑞霞 《精准医学杂志》 2024年第5期377-382,388,共7页
目的探讨瞬时受体电位阳离子通道6(TRPC6)对糖尿病肾病(diabetickidneydisease,DKD)小鼠肾小管间质炎症的影响及其机制。方法将6周龄雄性C57BL/6J小鼠36只随机分为6组,每组6只。对照组(A组)和DKD组(B组)分别腹腔注射0.1mmol/L柠檬酸盐... 目的探讨瞬时受体电位阳离子通道6(TRPC6)对糖尿病肾病(diabetickidneydisease,DKD)小鼠肾小管间质炎症的影响及其机制。方法将6周龄雄性C57BL/6J小鼠36只随机分为6组,每组6只。对照组(A组)和DKD组(B组)分别腹腔注射0.1mmol/L柠檬酸盐缓冲液和10g/L链脲佐菌素(后简称给药);DKD+生理盐水干预组(C组)和DKD+线粒体自噬激活剂干预组(D组)在B组基础上分别灌胃生理盐水和10mmol/L尿石素A;DKD+阴性对照慢病毒转染组(E组)和DKD+TRPC6敲降慢病毒转染组(F组)在B组基础上分别尾静脉注射阴性对照慢病毒和TRPC6敲降慢病毒。测定各组小鼠给药后第12周时的全血空腹血糖(FBG)水平、尿微量白蛋白肌酐比(ACR)和血尿素氮(BUN)水平,PAS染色观察小鼠肾小管损伤情况并进行评分,实时荧光定量PCR(RT-qPCR)技术检测小鼠肾组织中炎性因子(IL-1β、MCP-1、TNF-α)mRNA水平,免疫组织化学染色观察小鼠肾组织中TRPC6蛋白表达水平,蛋白免疫印迹检测小鼠肾组织中TRPC6、LC3B、P62、PINK1、Parkin相对表达量,透射电镜观察小鼠肾小管细胞中线粒体自噬体数量变化。将HK-2细胞分为高糖+TRPC6siRNA+DMSO干预组(G组,TRPC6siRNA转染+35.0mmol/L葡萄糖+0.06%DMSO)和高糖+TRPC6siRNA+线粒体自噬抑制剂干预组(H组,TRPC6siRNA转染+35.0mmol/L葡萄糖+12μmol/L千层纸素A),RT-qPCR技术检测细胞中炎性因子(IL-1β、MCP-1、TNF-α)mRNA的水平。结果给药后第12周时,B组小鼠全血FBG水平、ACR、BUN水平、肾小管损伤评分、肾组织炎性因子mRNA水平及TRPC6、P62蛋白表达水平均显著高于A组(t=2.77~13.61,P<0.05),肾组织LC3B-Ⅱ/LC3B-Ⅰ及PINK1、Parkin蛋白表达水平显著低于A组(t=3.33~14.63,P<0.05),肾小管细胞中线粒体自噬体数量减少;D组小鼠ACR、BUN水平、肾小管损伤评分、肾组织炎性因子mRNA水平及P62蛋白表达水平显著低于C组(t=2.40~23.50,P<0.05),肾组织LC3B-Ⅱ/LC3B-Ⅰ及PINK1、Parkin蛋白表达水平显著高于C组(t=5.74~12.50,P<0.05),肾小管细胞中线粒体自噬体数量增多;F组小鼠ACR、BUN水平、肾小管损伤评分、肾组织炎性因子mRNA水平及TRPC6、P62蛋白表达水平均显著低于E组(t=2.45~7.09,P<0.05),肾组织LC3B-Ⅱ/LC3B-Ⅰ及PINK1、Parkin蛋白表达水平显著高于E组(t=7.91~13.18,P<0.05),肾小管细胞中线粒体自噬体数量增多;H组细胞的炎性因子mRNA水平显著高于G组(t=5.40~7.27,P<0.05)。结论TRPC6可通过上调自身表达,抑制肾小管细胞线粒体自噬,从而加重DKD小鼠的肾小管间质炎症。TRPC6抑制药物有希望用于DKD治疗。 展开更多
关键词 糖尿病肾病 TRPC阳离子通道 线粒体自噬 肾炎 间质性 疾病模型 动物 小鼠 近交C57BL
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超极化激活的环核苷酸门控通道1参与七氟烷诱导的顺行性遗忘作用的机制研究
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作者 杨颖 钱彬 +1 位作者 陈思思 姚玉笙 《创伤与急诊电子杂志》 2024年第2期93-98,共6页
目的旨在探讨超极化激活的环核苷酸门控通道1(hyperpolarization-activated cyclic nucleotide-gated cation channel 1,HCN1)在七氟烷诱导的顺行性遗忘中的作用机制。方法采用雄性SPF级C57BL/6J野生型小鼠(WT组,n=60)和HCN1基因全身敲... 目的旨在探讨超极化激活的环核苷酸门控通道1(hyperpolarization-activated cyclic nucleotide-gated cation channel 1,HCN1)在七氟烷诱导的顺行性遗忘中的作用机制。方法采用雄性SPF级C57BL/6J野生型小鼠(WT组,n=60)和HCN1基因全身敲除(HCN1-/-)小鼠(HCN1-/-组,n=60)。将两组小鼠分别暴露于不同浓度的七氟烷(0%、0.1%、0.2%、0.4%、0.6%和0.8%)下,每个浓度10只小鼠。随后进行条件性恐惧实验,计算两组小鼠七氟烷抑制条件性恐惧记忆的半数效应浓度(median effective concentration,用EC50表示)。采用全细胞膜片钳技术记录0.125mmol/L七氟烷浓度灌流液对转染HCN1的人胚肾293细胞(HEK293-HCN1)上HCN1电流的影响,比较七氟烷处理前(Control组)和处理后(Sevoflurane组)HCN1电流的变化。结果与-/-WT组小鼠相比,HCN1组小鼠在七氟烷抑制场景恐惧记忆和声音恐惧记忆中的EC50值升高,差异有统计学意义(场景恐惧记忆:0.18%比0.26%,P<0.001;声音恐惧记忆:0.47%比0.49%,P<0.001)。全细胞电生理记录显示,与基础值相比,0.125mmol/L七氟烷抑制HEK293-HCN1细胞在﹣90~﹣140mV范围内的电流幅度(P值均<0.05),并增加了半最大激活电压(V1/2a)值[(﹣108±2.9)mV比(﹣100.1±3.0)mV,(P<0.001)]。结论HCN1电流的抑制可能参与了七氟烷诱导的顺行性遗忘作用。 展开更多
关键词 七氟烷 顺行性遗忘 超极化激活的环核苷酸门控阳离子通道 条件性恐惧实验 单细胞膜片钳
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电感耦合等离子体发射光谱法检测除盐水系统痕量阳离子
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作者 陈勇 《电工技术》 2024年第3期1-3,共3页
提出了采用电感耦合等离子体发射光谱仪(ICP-AES)测量除盐水中Ca、Mg、Al的方法,对分析条件进行优化,并对上述离子的方法检出限、准确度、回收率进行测定与评估。结果表明:ICP-AES法可快速、准确、稳定地测量除盐水中Ca、Mg、Al,其中各... 提出了采用电感耦合等离子体发射光谱仪(ICP-AES)测量除盐水中Ca、Mg、Al的方法,对分析条件进行优化,并对上述离子的方法检出限、准确度、回收率进行测定与评估。结果表明:ICP-AES法可快速、准确、稳定地测量除盐水中Ca、Mg、Al,其中各离子的方法检出限为Ca 0.5μg/L、Mg 0.5μg/L、Al 2μg/L,各离子的加标回收率在98%~102%,相对标准偏差均小于1.5%。所提方法弥补了3~6号机组除盐水制水系统新增Ca、Mg、Al等阳离子没有专门分析方法的不足,实现了一次进样同时检测多种离子,提高了对田湾核电站二期除盐水系统水质的检测能力,对后续除盐水系统调试、运行期间水质的分析具有重要意义。 展开更多
关键词 除盐水 ICP-AES 阳离子 回收率 方法检出限 多通道
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柯街河道断面水位流量关系单值化工程措施研究
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作者 阮良鸿 段奇涛 《水利信息化》 2024年第4期82-87,共6页
为掌握柯街河道断面工程措施后断面冲淤变化、水文要素测验条件和水位流量关系变化等水文特征规律,推进水文数据采集自动化,数据管理信息化、数字化、智慧化建设,开展柯街河道断面水位流量关系单值化工程措施研究。依据工程措施前后实... 为掌握柯街河道断面工程措施后断面冲淤变化、水文要素测验条件和水位流量关系变化等水文特征规律,推进水文数据采集自动化,数据管理信息化、数字化、智慧化建设,开展柯街河道断面水位流量关系单值化工程措施研究。依据工程措施前后实测水文资料,采用对比分析法和误差分析法,对工程措施实施效果进行统计分析。结果表明:工程措施实施后河道断面冲淤变化明显减小,水位及流量监测条件得到改善,水位流量关系变化趋于稳定,河道断面河段高洪水位至保证水位行洪能力降低6.4%~14.9%。柯街河道断面单值化工程措施效果明显,可为下一步工作的推进及河道断面单值化工程措施的应用推广和研究提供参考借鉴。 展开更多
关键词 河道断面 水位流量关系 单值化 工程措施
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