幽门螺杆菌对大鼠胃上皮细胞环氧合酶-2表达的影响

目的： 探讨幽门螺杆菌（Hp）水提取物对大鼠胃上皮细胞环氧合酶-2（COX-2）表达及前列腺素E₂（PGE₂）合成的影响。方法：大鼠胃上皮细胞株RGM1体外常规培养，Hp组细胞培养液内Hp水提取物终浓度为2.5 mg/L、5 mg/L、10 mg/L，大肠埃希菌组大肠埃希菌水提取物终浓度10 mg/L。培养 24 h 后收集细胞和上清液分别用于Western blotting分析COX-1、COX-2表达和酶免疫方法测定前列腺素E₂（PGE₂）含量。结果：Hp水提取物剂量依赖地增加RGM1细胞COX-2表达但不影响COX-1表达，而大肠埃希菌水提取物对COX-1和COX-2表达均无明显影响。RGM1细胞培养上清液中PGE₂水平在Hp组（2.5、5、10 mg/L）和大肠埃希菌组分别为（230.70±48.55）ng/g protein、（291.82±33.49）ng/g protein、（342.94±28.70）ng/g protein和（130.54±42.81）ng/g protein。结论：Hp体外诱导大鼠胃上皮细胞COX-2表达而增加PGE₂合成，Hp感染的致癌机制可能与其诱导的COX-2表达有关。     

宣痹汤通过调控COX-2信号通路抑制大鼠急性痛风性关节炎炎症反应的机制研究

目的：探究宣痹汤抑制环氧合酶-2(COX-2)通路对急性痛风性关节炎（GA）大鼠炎症的影响。方法：SD大鼠60只,随机分为对照组、模型组、塞来昔布组（20 mg/kg）、宣痹汤低剂量组（5 g/kg）、宣痹汤中剂量组（10 g/kg）、宣痹汤高剂量组（20 g/kg）,每组10只。采用Coderre经典方法建立大鼠痛风模型,对各组大鼠一般情况进行观察,步态分析,评估关节肿胀程度;利用HE染色技术对大鼠踝关节滑膜组织进行观察;ELISA测定大鼠关节液中炎症因子IL-1β、TNF-α、PGE2、LTB4水平;免疫印迹法检测大鼠踝关节滑膜组织PGE受体2(EP2)和LTB受体1(BLT1)的表达情况;qRT-PCR测定COX-2、5-脂氧合酶（5-LOX） mRNA表达的影响。结果：模型组大鼠关节肿胀、跛足、毛发暗淡、精神萎靡;塞来昔布组、宣痹汤低、中、高剂量组的大鼠症状明显改善;相比于对照组,模型组大鼠步态评价、关节肿胀程度、组织病理学改变、IL-1β、TNF-α、PGE2、LTB4、COX-2、5-LOX、EP2、BLT1水平显著升高（P<0.05）;与COX-2抑制剂塞来昔布组相...     

体外诱导骨髓间充质干细胞向心肌样细胞分化

目的 探讨生长因子在体外能否诱导大鼠骨髓来源的间充质干细胞（BM-MSC）向心肌样细胞分化,是否增强其旁分泌作用.方法 取4周龄雄性SD大鼠骨髓,贴壁法培养BM-MSC至第3代时,应用流式细胞仪检测其表面标志物CD29、CD44、CD105、CD34、CD45、CD31.将细胞随机分为间充质干细胞组（MSC组）和生长因子共培养组（GF-MSC组）.MSC组继续培养传代;GF-MSC组与生长因子[其中包括培养基（IMDM）、2％胎牛血清（FBS）、20 nmol/L地塞米松、100μmo1/L维生素C（VitC）、50 μg/L成纤维细胞生长因子2（FGF-2）、10 μg/L成骨蛋白2（BMP-2）、2μg/L胰岛素样生长因子1（IGF-1）、青霉素和100 mg/L链霉素]共培养.1周后细胞免疫荧光染色检测两组细胞肌钙蛋白Ⅰ（TnⅠ）和结蛋白（Des）表达;反转录-聚合酶链反应（RT-PCR）检测两组细胞Tn Ⅰ和Des mRNA的表达;ELISA法检测两组细胞裂解液以及细胞培养上清中的肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）的蛋白水平.结果 体外培养的BM-MSC表达CD29、CD44、CD105,而不表达CD31、CD34、CD45.免疫荧光染色显示GF-MSC阳性表达TnⅠ和Des.RT-PCR结果显示TnⅠ和Des mRNA在GF-MSC有阳性表达,而MSC为阴性表达.GF-MSC组HGF、VEGF在细胞裂解液和细胞培养上清中的蛋白水平（ng/L）高于MSC组（HGF裂解液32.05±0.41比12.10±0.21,培养上清574.21±4.19比169.16±2.41;VEGF裂解液45.66±2.22比30.37±0.54,培养上清487.78±36.29比44.25±1.31;均P＜0.05）.结论 体外与生长因子共培养,可诱导BM-MSC向心肌样细胞分化,并增强其旁分泌作用.     

IL-4下调COPD肺泡Ⅱ型上皮细胞中COX-2和PDGF的表达

目的：探讨COPD大鼠肺泡Ⅱ型上皮细胞（ATⅡ）中环氧合酶-2（COX-2）及血小板源性生长因子（PDGF）的表达及IL-4对其表达的影响。方法：用雄性Wistar大鼠建立吸烟大鼠COPD模型后取整肺做原代培养，培养出肺泡Ⅱ型上皮细胞。随机分为对照组和模型组，并用IL-4干预模型组的肺泡Ⅱ型上皮细胞。用免疫组化法检测细胞爬片COX-2、PDGF-A及PDGF-B的表达。结果：模型组COX-2和PDGF-A、PDGF-B表达明显增高；IL-4干预组表达显著降低。结论：COPD大鼠肺泡Ⅱ型上皮细胞中COX-2和PDGF的表达显著增高，IL-4可降低其表达。     

肾上腺素对小鼠巨噬细胞中促炎／抗炎介质比值的影响

目的：研究肾上腺素对脂多糖（LPS）诱导的小鼠单核巨噬细胞株RAW264.7中促炎介质［肿瘤坏死因子（TNF-α）、一氧化氮（NO）、环加氧酶-2（COX-2）］和抗炎介质［血红素氧化酶-1（HO-1）、白介素10（IL-10）］表达及NF-κB活化的影响。 方法： 以10 μg/L的LPS刺激体外培养的RAW264.7细胞作为炎症模型，加入不同浓度的肾上腺素（1、5、10、50 μmol/L）孵育24 h后，收集培养上清并提取细胞总蛋白，酶联免疫法测定上清中TNF-α、IL-10浓度，Griess法检测上清NO含量(以NO2-/NO3-表示)，免疫印迹法检测细胞总蛋白中COX-2、HO-1、IκB-α的含量。 结果： 10 μg/L的LPS明显诱导TNF-α、NO(NO2-/NO3-)、COX-2、IL-10及HO-1的产生；LPS+肾上腺素组与LPS单独作用组相比促炎介质TNF-α、NO(NO2-/NO3-)、COX-2的表达量显著下降，而抗炎介质IL-10、HO-1的表达却明显增强；肾上腺素与LPS共同作用组中IκB-α的含量与单独LPS作用组相比无明显差异。 结论： 肾上腺素下调LPS诱导的巨噬细胞中促炎介质的表达同时促进抗炎介质的表达，这种效应并不通过影响NF-κB的活化来实现。     

环氧合酶-2抑制剂对盐酸诱导大鼠胃粘膜损伤后上皮细胞增殖和愈合的影响

目的:探讨特异性和非特异性环氧合酶-2(COX-2)抑制剂,对盐酸诱导胃粘膜损伤后上皮细胞增殖和损伤愈合的影响。方法:大鼠胃内给予06mol/LHCl1mL后,胃内给予NS-398或吲哚美辛,Westernblot和免疫组化法分析盐酸灌胃前、后胃粘膜COX-2表达,免疫组化检测增殖细胞核抗原(PCNA)评价上皮细胞的增殖状态,小格图纸法计算胃损伤指数(LI)。结果:盐酸灌胃后,COX-2在胃粘膜表层上皮细胞和腺颈部成体干细胞高表达。盐酸灌胃后24h,NS-39840mg/kg组及吲哚美辛组PCNA标记指数(PCNA-LI)分别为(22.72±4.33)%和(21.98±5.18)%,明显低于对照组(34.46±3.61)%(P<0.05);NS-3984mg/kg组和40mg/kg组LI分别为(1.28±0.58)%和(1.16±0.56)%,显著高于对照组(0.58±0.24)%(P<0.05)。结论:COX-2抑制剂抑制胃粘膜上皮细胞增殖,延迟大鼠胃粘膜损伤的愈合,提示COX-2表达在胃粘膜再生过程中起重要作用。     

阿托伐他汀对糖尿病大鼠急性心肌梗死后心功能及HGF/c-Met信号通路的影响*

 目的： 糖尿病患者急性心肌梗死（AMI）后的心室重构及心功能恶化较非糖尿病者更为明显。本研究旨在观察阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能的影响,并探讨其作用是否与肝细胞生长因子及其受体 (HGF/c-Met)信号通路有关。方法: 70只雄性SD大鼠经链脲霉素 (STZ, 65 mg/kg)腹腔注射,诱导糖尿病大鼠模型。8周后对糖尿病大鼠结扎左冠状动脉前降支构建AMI大鼠模型,术后存活32只大鼠随机分为2组：AMI对照组(n=16)和阿托伐他汀干预组(n=16, 阿托伐他汀20 mg·kg-1·d-1),并在糖尿病大鼠中设假手术组(n=11),术后24 h予以灌胃给药。2周后比较各组大鼠心功能、心肌组织病理改变、心肌细胞凋亡、HGF和c-Met mRNA及蛋白表达差异。结果: (1) AMI对照组心功能显著低于假手术组（P<0.05）,胶原容积分数、心肌细胞凋亡指数、HGF及c-Met mRNA及蛋白表达均显著高于假手术组（P<0.05）;(2) 阿托伐他汀干预组的胶原容积分数和心肌细胞凋亡指数显著低于AMI对照组（P<0.05）,心功能、HGF及c-Met mRNA及蛋白表达均显著高于AMI对照组（P<0.05）。结论: 阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能具有显著改善作用;HGF/c-Met信号通路在AMI后会激活,阿托伐他汀的上述作用机制可能与其进一步增强HGF/c-Met信号通路有关。     

糖尿病大鼠心肌NF-κB、iNOS、COX-2表达的研究

目的：观察核因子-κＢ（ＮＦ-κＢ）、诱导型一氧化氮合酶（iNOS）以及环氧化酶-2（COX-2）3种炎症因子在糖尿病大鼠心肌组织的表达。方法:30只SD大鼠随机分为正常对照组和糖尿病组，糖尿病组大鼠按60 mg/kg的剂量1次性腹腔注射链脲菌素。实验于24周末结束，观察2组大鼠的体重、平均血糖浓度、心重指数。并取心肌组织石蜡切片分别行NF-κＢ、iNOS和COX-2免疫组化染色。同时用凝胶电泳迁移率（EMSA）的方法测定心肌组织ＮＦ-κＢ活性。结果:(1)糖尿病大鼠心肌组织ＮＦ-κＢ阳性表达细胞明显多于对照组；（2）EMSA方法显示，糖尿病大鼠心肌组织ＮＦ-κＢ表达强度明显高于对照组；（3）对照组大鼠心肌组织未见iNOS的表达，糖尿病大鼠见明显iNOS的表达；（4）对照组大鼠心肌组织偶见COX-2的表达，糖尿病大鼠见明显COX-2的表达。结论:NF-κＢ、iNOS和COX-2在糖尿病大鼠心肌组织中表达活性明显增强。     

肝素、IGFBP-4及IGF-1对肺成纤维细胞糖代谢及功能的影响

目的：探讨类胰岛素生长因子（IGF-1）及其结合蛋白-4（IGFBP-4）、肝素在肺纤维化形成过程中的相互关系。方法：选择二倍体人胚肺成纤维细胞（lung fibroblast,LF）株，分别给予100 μg/L IGF-1、100 μg/L IGF-1+100 μg/L IGFBP-4、100 μg/L IGF-1+200 μg/L IGFBP-4、100 μg/L IGF-1+100 μg/L IGFBP-4+100 μg/L肝素、100 μg/L IGF-1+100 μg/L IGFBP-4+200 μg/L肝素、100 μg/L IGF-1+100 μg/L肝素、100 μg/L IGF-1+200 μg/L肝素刺激24 h。检测细胞外弹性蛋白、胶原蛋白及细胞内葡萄糖转运蛋白-4（GLUT-4）、己糖激酶-2（HK-2）的含量。结果：与空白对照组相比，IGF-1组HK-2及GLUT-4mRNA及相应蛋白表达增强（P<0.05）；加入IGFBP-4以后HK-2及GLUT-4mRNA及相应蛋白表达明显强于IGF-1组（P<0.05）；而同时加入肝素与IGFBP-4后HK-2及GLUT-4mRNA及相应蛋白表达明显抑制（P<0.05），并且这一抑制效应随肝素用量增加而更加明显；但单加肝素时HK-2及GLUT-4mRNA及相关蛋白表达抑制不如前组明显（P<0.05）。结论：（1） IGF-1能够刺激肺成纤维细胞的糖代谢，使HK-2及GLUT-4mRNA及细胞外基质（ECM）蛋白表达增强；（2）单纯增加IGFBP-4不仅不能抑制IGF-1的刺激作用，反而增加HK-2及GLUT-4mRNA及相应蛋白表达，可能与IGFBP-4的降解有关；（3）IGFBP-4在肝素存在的情况下，能明显抑制IGF-1对肺成纤维细胞的刺激作用，使HK-2及GLUT-4及细胞外基质蛋白表达明显减少，说明肝素以及未被降解的IGFBP-4对肺纤维化可能是有效的防护因子。     

肝再生增强因子对外原性抗原引起机体免疫应答影响的研究

目的 研究rALR对HBsAg及BSA免疫大鼠产生抗体、细胞因子和对脾脏细胞增殖的影响.方法 甲醇诱导表达rALR,测定活性并进行以下研究.①rALR对HBsAg免疫的影响:实验分为:生理盐水、HBsAg20 μg/只、HBsAg20 μg rALR100 μg/kg、HBsAg20 μg rALR 25 μg*kg、HBsAg20 v pPIC9K表达上清、HBsAg20 μg CsA10mg/kg,共6组;②rALR对BSA免疫的影响:实验分为:生理盐水、BSA25 μg/只、BSA25 μg rALR100 μg/kg、BSA25 μg pPIC9K表达上清、BSA25 μg CsA10 mg/kg,共5组.以上均皮下注射免疫大鼠,1次/周×4次,ELISA检测血清中相应抗体、IL-2和IFN-γ.③rALR对大鼠脾细胞增殖的影响:Wisar大鼠先皮下注射HBsAg(20 μg/只)1次,2周后处死,分离脾单核细胞,种板,再加HBsAg 1 μg/孔和/或相应处理因素(rALR、空质粒表达产物等),48h后加3H-TdR,12 h后收集细胞,检测cpm值.结果 rALR100 μg/kg HBsAg组的8只动物中,有2只出现抗HBs的抗体,空质粒对照组和单用HBs Ag组8只动物均出现抗HBs.rALR 100 μg/kg BSA组的8只动物中,有3只出现抗BSA抗体,空质粒对照组和单用BSA组8只动物均出现抗BSA的抗体.rALR 100μg/kg能明显抑制细胞因子IL2及IFN-γ的产生.rALR4μg体外能明显抑制脾细胞的增殖.结论 rALR能抑制HBsAg和BSA诱导大鼠产生相应抗体及IL-2、IFN-γ的产生;体外能抑制经体内致敏的脾细胞的增殖,说明rALR有免疫抑制作用.     

Selective cyclooxygenase-2 blocker delays healing of esophageal ulcers in rats and inhibits ulceration-triggered c-Met/hepatocyte growth factor receptor induction and extracellular signal-regulated kinase 2 activation

Nonsteroidal anti-inflammatory drugs, both nonselective and cyclooxygenase-2 (COX-2) selective, delay gastric ulcer healing. Whether they affect esophageal ulcer healing remains unexplored. We studied the effects of the COX-2 selective inhibitor, celecoxib, on esophageal ulcer healing as well as on the cellular and molecular events involved in the healing process. Esophageal ulcers were induced in rats by focal application of acetic acid. Rats with esophageal ulcers were treated intragastrically with either celecoxib (10 mg/kg, once daily) or vehicle for 2 or 4 days. Esophageal ulceration triggered increases in: esophageal epithelial cell proliferation; expression of COX-2 (but not COX-1); hepatocyte growth factor (HGF) and its receptor, c-Met; and activation of extracellular signal-regulated kinase 2 (ERK2). Treatment with celecoxib significantly delayed esophageal ulcer healing and suppressed ulceration-triggered increases in esophageal epithelial cell proliferation, c-Met mRNA and protein expression, and ERK2 activity. In an ex vivo organ-culture system, exogenous HGF significantly increased ERK2 phosphorylation levels in esophageal mucosa. A structural analog of celecoxib, SC-236, completely prevented this effect. These findings indicate that celecoxib delays esophageal ulcer healing by reducing ulceration-induced esophageal epithelial cell proliferation. These actions are associated with, and likely mediated by, down-regulation of the HGF/c-Met-ERK2 signaling pathway.     

Nonsteroidal anti-inflammatory drugs for treatment of advanced gastric cancer: cyclooxygenase-2 is involved in hepatocyte growth factor mediated tumor development and progression

Surgical treatment of gastric cancer patients is dismal because advanced tumor is often noted at diagnosis. In order to obtain better adjuvant therapy for gastric cancer patients after operation, it is important to understand the mechanism of invasion and metastasis. It is well known that binding of hepatocyte growth factor (HGF) to its receptor (c-Met) regulates gastric cancer progression and metastasis. Recently, HGF was found to up-regulate the expression of cyclooxygenase-2 (COX-2) gene and increase prostaglandin (PG)synthesis in gastric mucosa cells. Over-expression of COX-2 and increased PG secretion have also been found to be involved in the growth and metastasis of gastric cancer. These results together suggest that the signaling pathway of HGF and c-Met may be mediated through ERK2 activation, up-regulation of COX-2 and increased production of PGE(2)in gastric cancer cells. In view of the fact that c-Met is over-expressed in the majority of gastric cancer patients with poor prognosis, COX-2 specific inhibitors may provide beneficial effects in these patients.     

The effects of gastrin on the ultrastructure of rat stomach endocrine cells

The effects of a single injection of gastrin on rat gastric endocrine cells were examined ultrastructurally and as a corollary serum gastrin was measured by radioimmunoassay. Eight fasting inbred rats received single subcutaneous injections of Pentagastrin (300 μg/kg) over a period of 24 hr. Gastric mucosa and blood were obtained from the rats which were sacrificed from 15 min to 24 hr after gastrin administration. At 30 min, serum gastrin was elevated to a peak of 321 pg/ml. ECL cells showed ultrastructural evidence of histamine release at 15 and 30 min. Somatostatin D and ECL cells both showed exocytotic figures at the same times. Evidence of granule release was rarely seen in the EC cells and hardly ever found in the G and A-like (or X) cells.     

Mucosal expression of cyclooxygenase isoforms 1 and 2 is increased with worsening damage to the gastric mucosa

AIMS : To test the hypothesis that both COX-1 and COX-2 expression in human gastric mucosa is up-regulated in the presence of inflammation as seen in patients with gastritis and gastric ulcers. METHODS AND RESULTS: We performed immunohistochemistry using COX-1 and COX-2 monoclonal antibodies on gastric biopsies from 59 patients with normal mucosa, gastritis and gastric ulcers. Expression of COX-1 and COX-2 was quantified using an intensity proportion scoring system. Expression of COX-1 was primarily seen in the lamina propria mononuclear cells with some expression in deep gastric glands in the ulcer group. Expression of COX-2 was primarily seen in the deep gastric glands with focal expression in the lamina propria mononuclear cells. We found a stepwise increase in the expression of both COX-1 and COX-2 as mucosal damage progressed from normal to gastritis to gastric ulcer. CONCLUSIONS: We conclude that both COX-1 and COX-2 expression in the gastric mucosa are increased in the setting of gastritis and gastric ulceration. Although this increased expression may be due, at least in part, to an increase in inflammatory cell numbers, this study raises the possibility that both COX-1 and COX-2 are inducible, contrary to the traditionally held view of only COX-2 being inducible.     

JTE-522 selectively inhibits cyclooxygenase-2-derived prostaglandin production in inflammatory tissues

OBJECTIVE AND DESIGN: To investigate the effect of JTE-522, a selective cyclooxygenase (COX)-2 inhibitor, on prostaglandin (PG) production and COX expression in rats. SUBJECTS: Male rats (4-8 weeks old) were used for in vivo experiments, while for in vitro assay, rat peritoneal macrophages were used. TREATMENT: JTE-522 (1-100 mg/kg) and indomethacin (0.03-10 mg/kg) were administered orally. JTE-522 and reference compounds (0.01-10 microM) were subjected to COX expression. RESULTS: JTE-522 inhibited the development of carrageenin-induced paw edema and PGE2 production in inflammatory paws at a dose of 10 mg/kg. On the other hand, JTE-522 (1-100 mg/kg) did not affect A23187-stimulated thromboxane B2 release from whole blood or the PGE2 level in gastric mucosa. JTE-522 did not suppress lipopolysaccharide-induced COX-2 expression in peritoneal macrophages. CONCLUSION: These results indicate that JTE-522 selectively inhibits PG production mediated by COX-2 in inflammatory tissues. JTE-522 may thus represent a novel type of anti-inflammatory drug without adverse effects on the gastro-intestinal tract.     

Comparison of the ECL-cell frequency in the stomachs of 3 different rat strains.

Three different rat strains, Sprague-Dawley, Wistar and Fischer 344, were treated for 3 months with 2 doses (0.8; 4 mg/kg) of the gastric acid suppressing ATPase inhibitor pantoprazole. The gastrin levels were determined, the height of the mucosa measured and the number of enterochromaffin-like (ECL) cells counted. Because these cells were stained according to the method of Grimelius they were designated as GPC (Grimelius positive cells). Under 4 mg/kg, the gastrin levels were increased 8 hours after administration, but fell again after 24 h. The Fischer rats showed the highest value. Also the height of the mucosa was increased under 4 mg/kg. A trend towards an increased mucosal height was noticeable even at 0.8 mg/kg. The number of GPC was determined in 2 ways: 1) without taking the mucosal height into account, 2) taking the height into account. An increase in GPC was observed at 4 mg/kg with both methods.     

Growth factors expression in patients with erosive esophagitis

Although the pathogenesis and treatment of erosive esophagitis (EE) is well recognized, little is known about the cellular and molecular mechanisms of mucosal healing in EE patients. In this pilot study, we enrolled typical EE patients to evaluate what kinds of growth factors and their receptors were activated in their injured esophageal mucosa. Forty endoscopically proved EE patients were consecutively enrolled. Messenger RNA expressions, which includes keratinocyte growth factor (KGF) and its receptor (KGFR), epidermal growth factor (EGF) and its receptor (EGFR), hepatocyte growth factor (HGF) and its receptor (HGFR), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and cyclooxygenase (COX)-1 and COX-2, were measured using real-time polymerase chain reaction (PCR). Data were compared between the injured EE mucosa and their normal esophageal mucosa above EE. The mRNA expressions of HGF, HGFR, EGF, VEGF, and COX-2, but not EGFR, KGF, KGFR, bFGF, and COX-1, were significantly increased in the injured mucosa of EE patients compared with those of normal mucosa (P < 0.05). The study found that HGF, HGFR, EGF, VEGF, and, COX-2 are activated in the injured mucosa of EE patients; their activation might be involved in mucosal repair and ulcer healing of EE.     

雷公藤甲素对LPS诱导的海马炎症过程中COX-2和iNOS表达的影响

选用健康成年雄性SD大鼠,用不同剂量(10μg·kg-1·d-1,25μg·kg-1·d-1,50μg·kg-1·d-1)的雷公藤甲素预处理5d后,立体定位海马注射脂多糖(LPS),采用免疫组织化学染色方法观察海马CA3区环氧化酶2(COX-2)和诱导型一氧化氮合酶(iNOS)的表达变化。结果发现:与注射生理盐水对照组比较,注射LPS可引起海马CA3区的COX-2和iNOS显著表达,而雷公藤甲素(50μg·kg-1·d-1)可明显下调LPS诱导的COX-2和iNOS的表达,其抑制程度与药物剂量呈正相关。本实验结果提示雷公藤甲素对中枢神经系统中LPS诱导的COX-2和iNOS的表达有明显的抑制作用。     

The protective effects of calcitonin gene-related peptide on gastric mucosa injury of gastric ischemia reperfusion in rats

Gastric mucosa is one of the most vulnerable tissues in human and animal. However, little is known about the effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injuries induced by gastric ischemia reperfusion. The purpose of the present study was to investigate the protective effects and mechanism of CGRP on gastric mucosa injury after gastric ischemia reperfusion in rats. Thirty-six healthy Wistar rats were randomly divided into CGRP-treated, sham-operated, and control groups. Twelve rats were involved in each group. These groups were further divided into 24-h and 48-h subgroups. Gastric ischemia reperfusion injury (GI-RI) rat model was established by a 30-min celiac artery occlusion by an artery clamp, followed by 24?h or 48?h of reperfusion. CGRP (1?μg/ml) at the dose of 3?μg/kg was given intraperiloneally (IP) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3?ml/kg body weight), IP, was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without GI-RI. Twenty-four hours or 48?h after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy and observing the expression of gastrin (Gas) and somatostatin (SST) by immunohistochemical staining. The results showed the following: (i) gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, and infiltration of inflammatory cells were observed in both control and CGRP-treated animals, especially in the earlier period (24?h) and then gradually healing. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P?<?0.01). (ii) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P?<?0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P?<?0.01). It is concluded that CGRP regulated the secretion of Gas and SST and thus alleviated the damage of gastric mucosa induced by ischemia and reperfusion. CGRP might be a potential candidate for clinical therapy on modulating gastric mucosal protection and maintaining gastric mucosal integrity after ischemia and reperfusion of the stomach.