氯吡格雷对大鼠急性胃黏膜损伤愈合的影响及机制

目的:研究氯吡格雷对大鼠急性胃黏膜损伤愈合的影响作用及其机制.方法:40只健康♂SD大鼠随机分为4组,每组10只:阴性对照组、单纯损伤组、10mg/kg氯吡格雷处理组、30mg/kg氯吡格雷处理组;以大剂量阿司匹林灌胃制造大鼠急性胃黏膜损伤模型后,对氯吡格雷处理组的大鼠以相应剂量的氯吡格雷进行灌胃处理,给药3d,每天1次.分别测定各组大鼠的胃黏膜损伤指数(lesionindex,LI);观察大鼠胃黏膜组织学变化;免疫组织化学法检测各组紧密连接蛋白Occludin的表达情况;免疫蛋白印迹法(Westernblot)检测紧密连接蛋白Occludin、ZO-1以及MAPK信号通路中磷酸化P38、磷酸化ERK及磷酸化JNK蛋白的表达量.结果:与损伤组相比,氯吡格雷处理组大鼠胃黏膜损伤加重,且30mg/kg组损伤重于10mg/kg组(39.8±5.05vs35.3±3.86,P<0.05);在阴性对照组、单纯损伤组、10mg/kg氯吡格雷处理组、30mg/kg氯吡格雷处理组中,大鼠胃黏膜中的紧密连接蛋白Occludin、ZO-1蛋白的表达逐渐下降,呈递减趋势(P=0.000),而磷酸化P38、磷酸化ERK蛋白表达则逐渐上升,呈递增趋势(P=0.000).结论:氯吡格雷能够抑制大鼠急性胃黏膜损伤的愈合,其可能是通过激活MAPK中的p38和ERK信号通路,下调胃黏膜上皮细胞间紧密连接蛋白Occludin和ZO-1的表达,破坏大鼠胃黏膜的屏障.     

替普瑞酮对阿司匹林致胃黏膜损伤的保护作用

目的 研究替普瑞酮对阿司匹林所致胃黏膜损伤的保护作用.方法 2008年至2010年在浙江省中医院心血管科住院的首次服用常规剂量阿司匹林的患者296例,随机分为两组.阿司匹林组166例,每日服用阿司匹林肠溶片100 mg;阿司匹林+替普瑞酮组130例,在等同于阿司匹林组服用阿司匹林剂量的基础上,口服替普瑞酮舒50 mg/次,3次/d.分别观察两组患者3个月、6个月及1年后消化道症状和胃黏膜的损害情况.结果 阿司匹林组入组143例,阿司匹林+替普瑞酮组入组118例.服药3个月后阿司匹林组消化道症状的发生率为1.40％,与阿司匹林+替普瑞酮组比较差异有统计学意义(0,x2=1.663,P=0.197).服药6个月后随访,阿司匹林组消化道症状的发生率为4.96％,与阿司匹林+替普瑞酮组比较差异有统计学意义(0,x2=6.021,P＝0.014).服药1年后随访,阿司匹林组消化道症状的发生率为20.15％,与阿司匹林+替普瑞酮组比较差异有统计学意义(1.69％,x2=20.984,P=0.001).阿司匹林+替普瑞酮组随访6个月及1年后症状和胃镜积分与阿司匹林组相比明显降低(P值分别＜0.05和0.01).阿司匹林组1年后症状和胃镜积分与6个月时相比明显增高(P值分别＜0.05和0.01).结论 替普瑞酮对阿司匹林所致胃黏膜损伤有一定的保护作用.长期服用常规剂量的阿司匹林会引起胃黏膜不同程度的损害,胃黏膜损害的发生会随着服药时间增加而增加.     

环氧合酶-2抑制剂对大鼠胃黏膜损伤愈合的影响

目的　环氧合酶 (COX)是合成前列腺素 (PGs)的关键酶 ,传统的非甾体抗炎药 (NSAIDs)抑制COX 1和COX 2活性 ,引起严重的胃肠道不良反应。特异性COX 2抑制剂有望成为不引起胃损伤的新型NSAIDs。本研究探讨特异性和非特异性COX 2抑制剂对盐酸诱导大鼠胃黏膜损伤愈合的影响。方法　雄性SD大鼠胃内给予 0 .6mol/LHCl1ml,Westernblot和免疫组化法分析胃黏膜COX 1和COX 2表达。盐酸灌胃后 10min ,实验组胃内给予NS 3980 .4、4、4 0mg/kg和吲哚美辛 4 0mg/kg ,对照组胃内给予 1%阿拉伯树胶 (AG) 5ml/kg。盐酸灌胃前和灌胃后 1、3、6、12、2 4及 4 8h分别处死大鼠 ,剖腹取胃 ,观察各组动物损伤指数 (LI)及光镜下的胃黏膜病理学改变。结果　盐酸灌胃后COX 2在表层上皮细胞和颈黏液细胞表达显著增加 ,NS 398和吲哚美辛均延迟胃黏膜损伤的愈合。盐酸灌胃后 12h ,NS 398组 (4和 4 0mg/kg)及吲哚美辛组的LI分别为 (1.4 2± 0 .2 3) % ,(1.4 2± 0 .2 9) %和 (1.6 2± 0 .4 4 ) % ,明显高于对照组的 (0 .5 8± 0 .2 4 ) % (P <0 .0 5 )。结论　特异性和非特异性COX 2抑制剂延迟大鼠胃损伤后的愈合 ,提示COX 2表达在胃黏膜再生过程中起重要作用     

Protective effect of cimetidine on aspirin-induced gastric mucosal damage.

Aspirin alters the gastric mucosal barrier as measured by ionic flux and potential difference. The effect of cimetidine on aspirin-induced alterations in gastric mucosa was studied in five normal male volunteers. Aspirin effects were studied with and without previous treatment with cimetidine. Mean (+/- SEM) basal potential difference was -48 +/- 1 mV. After 600 mg of aspirin in 1 dl of isotonic saline, potential difference decreased in 10 min to -39 +/- 1 mV (P less than 0.001) and returned to baseline within 60 min. Control biopsies showed 2% damaged mucosal cells compared with 20% damaged at the time of maximal drop in potential difference (P less than 0.001) after aspirin. Recovery to 9% damage occurred by 60 min. In subjects pretreated with 300 mg cimetidine, potential difference rose during 1 h to -62 +/- 1 mV (P less than 0.001). After aspirin potential difference fell to -48 +/- 1 mV compared with -39 +/- 1 mV with aspirin alone (P less than 0.01) and returned to -62 +/- 1 mV at 60 min. The cimetidine-treated group showed 4% mucosal damage at the peak potential difference fall after aspirin, significantly less (P less than 0.02) than in the untreated subjects.     

潘托拉唑对胃黏膜损伤保护作用及其机制

目的:探讨潘托拉唑对大鼠胃黏膜损伤保护的作用及其机制.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予(iv)潘托拉唑(20mg/kg)、L-硝基-精氨酸甲酯(L-NAME,4mg/kg)及L-精氨酸(250mg/kg).采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2/NO-3含量,并观察了胃黏膜损伤指数(ulcerindex,UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,潘托拉唑组大鼠UI明显降低(5.7±2.1vs25.4±2.5,P<0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻.预先用L-NAME处理后,潘托拉唑保护胃黏膜损伤作用明显减弱;L-NAME抑制作用可被L-精氨酸拮抗.iv潘托拉唑,可增加GMBF、胃黏膜和血浆NO-2/NO-3,L-NAME可逆转这种作用,但对潘托拉唑抑制酸分泌作用无明显影响.结论:潘托拉唑通过一氧化氮介导对大鼠胃黏膜损伤有重要的保护作用,而与潘托拉唑抑制酸分泌作用无关.     

热休克预处理对大鼠烧伤后急性胃黏膜损伤的保护作用

目的观察热休克预处理对严重烧伤大鼠胃黏膜的影响。方法热休克预处理诱导热休克蛋白产生,然后制作烧伤大鼠急性胃黏膜损伤模型,进行胃黏膜损伤指数评分。运用免疫组化方法,检测胃黏膜热休克蛋白的表达,并进行图像分析。结果热休克预处理组胃黏膜损伤积分显著低于对照组(P<0.01)。免疫组化分析显示其胃黏膜热休克蛋白表达较对照组明显增强(P<0.01)。结论热休克预处理对烧伤大鼠胃黏膜具有保护作用,其保护机制可能与热休克蛋白诱导表达增强有关。     

Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE₂ (dmPGE₂: 3 and 10 g/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) at the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE₂. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE₂ has a unique protective ability that is not shared by usual cytoprotective agents.     

Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats.

Quantitative changes of gastric mucosal glycoproteins with the gastric damage induced by acetylsalicylic acid (aspirin) in rat have been studied. Gastric injury was easily observed macroscopically within one hour after the oral administration of aspirin. The most striking changes occurred at five hours, and the injury was overcome within nine hours after dosing. The glycoproteins extracted from rat stomack with Tris buffer containing Triton X-100 were fractionated on Bio-Gel A-1.5 m column chromatography and divided into three fractions. The first peak, corresponding to gastric mucus macromolecular neutral and acidic glycoproteins with or without sulphate (Fr.I), was diminished after aspirin administration. A considerable alteration of Fr.I (49% of control) appeared at three hours, and a gradual return to the control value was observed subsequently. The changes in the amount of the glycoproteins were detected before the macroscopical changes of the mucosa. These results suggest that gastric ulceration induced by aspirin may be caused by a deficiency of gastric mucus macromolecular glycoproteins of gastric mucus.     

埃索美拉唑对胃黏膜的保护作用及其机制

目的:探讨埃索美拉唑对大鼠胃黏膜保护的作用及其机制.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予埃索美拉唑(20 mg/kg)灌胃,L-硝基-精氨酸甲酯(L-NAME,4 mg/kg)和L-精氨酸(250 mg/kg)iv.采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),镉粒还原和比色法测定胃黏膜和血浆NO-2/NO-3含量,并观察胃黏膜损伤指数(ulcer index,UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,埃索美拉唑组大鼠UI明显降低(5.6±2.2 vs 25.3±2.4,P＜0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(P＜0.01).预先用L-NAME处理后,埃索美拉唑保护胃黏膜损伤作用明显减弱;L-NAME抑制作用可被L-精氨酸拮抗.向胃内灌注埃索美拉唑,可增加GMBF、胃黏膜和血浆NO-2/NO-3,L-NAME可逆转这种作用,但对埃索美拉唑抑制酸分泌作用无明显影响.结论:埃索美拉唑通过NO介导对大鼠胃黏膜损伤有重要的保护作用,而与埃索美拉唑抑制酸分泌作用无关.     

Protective effects of the whisky congeners on ethanol-induced gastric mucosal damage

BACKGROUND: The ingestion of both ethanol and whisky can induce acute gastrointestinal bleeding. The effects of the congeners, substances other than ethanol in whisky, on the ethanol-induced gastric mucosal damage were examined in the rat model. METHODS: After the whisky congeners were intragastrically administered previous to or simultaneous with ethanol ingestion, the gastric damage was macroscopically and microscopically measured. RESULTS: The simultaneous administration of the whisky congeners at a dose of 5 mg/kg body weight, which corresponds to the concentration of congeners contained in whisky, with 50% ethanol did not inhibit the hemorrhagic lesions, but inhibited them at a dose of 150 mg/kg. The treatment with the whisky congeners 30 minutes before the ethanol ingestion prevented the ethanol-induced gastric damage in a dose-dependent manner at 0.5 to 150 mg/kg. The butanol extract of the congeners revealed the strongest prevention compared with the ethyl acetate extract or the water fraction. The administration of indomethacin 60 minutes before the congener treatment partly inhibited the protective effects of the congeners, indicating the partial contribution of prostaglandins in this mechanism. The congeners did not prevent the mucosa by action as a "mild irritant" because the immunohistochemical studies using the antimucin monoclonal antibodies showed that no damage was induced by the administration of the congeners. CONCLUSION: The present results showed that the whisky congeners have a protective activity against ethanol-induced gastric mucosal injury.     

Protective effect of melatonin against multistress condition induced lipid peroxidation via measurement of gastric mucosal lesion and plasma malondialdehyde levels in rats

INTRODUCTION It has been accepted that the pathogenesis of ulcer is complex and related to different pathogenic factors. The most common side-effect of indomethacin (NSAID) is gastric mucosal damage. The inhibition of the biosynthesis of gastric prostagla…     

应激大鼠胃黏膜氧化应激指标受褪黑素影响的研究

目的探讨褪黑素干预应激大鼠胃黏膜氧化应激指标影响的研究.方法采用浸水-束缚(WIR)应激实验复制大鼠应激性溃疡模型.应激前30 min,MT(melatonin)5、20mg·kg-1和应激组大鼠分别腹腔注射MT 5、20mg·kg-1和等体积生理盐水.应激6h后,观察各组大鼠胃黏膜病变情况,对溃疡指数(UI)进行评分,同时检测各组大鼠胃黏膜内丙二醛(MDA)含量、胃黏膜超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)水平.结果WIR应激6h后,应激组大鼠胃黏膜MDA水平显著高于对照组(P＜0.01).MT 5、20mg·kg-1组较应激组MDA水平显著下降(P＜0.01),且MT 20mg·kg-1组显著低于MT 5mg·kg-1组(P＜0.01).应激组大鼠SOD、GSH活性较对照组明显降低(P＜0.01),MT 5、20mg·kg-1组较应激组SOD、GSH活性有升高趋势.比较各组UI发现,MT 5、20mg·kg-1组UI显著低于应激组(P＜0.01),其中MT 20mg·kg-1组UI显著低于MT 5mg·kg-1组(P＜0.05).结论褪黑素通过其抗氧化的作用对应激大鼠胃黏膜损伤起保护作用.     

Effects of blood glucose levels on aspirin-induced gastric mucosal damage

In female rats aspirin-induced gastric mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis.In vitro incubation of gastric mucosal homogenates showed that dibutyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.     

Protective role of metallothionein in stress-induced gastric ulcer in rats

AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO_4 (an MT inducer) treatment, WIR+ZnSO_4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO_4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.     

Influence of Bacterial Lipopolysaccharide on Healing of Chronic Experimental Ulcer in Rat

Background: Lipopolysaccharides (LPS) are major components of the outer membrane of Gramnegative bacteria, which play a central role as potent endotoxins in the pathogenesis of the Gram-negative septicaemia. Although it is well known that large amounts of endotoxin may produce haemorrhagic lesions in the stomach, the effect of LPS on ulcer healing has not been fully clarified. The aim of the present study was to examine the effect of parenteral injection of LPS at different doses on the course of ulcer healing in rats. Methods: Gastric ulcers were induced in Wistar rats by serosal application of an acetic acid area. After ulcer induction, vehicle (saline) or E. coli -LPS was injected at various doses (0.1, 1 and 5 mg/kg i.p.) for 7 days. The animals were sacrificed on day 8 after ulcer induction and the following parameters were analysed; ulcer area (planimetry), gastric blood flow (GBF) (H 2 gas clearance method), gastric secretion, plasma levels of proinflammatory cytokines such as IL-1 β and TNF α , mucosal gene expression for cyclooxygenases (COX-1/-2), apoptosis-related proteins (Bax, Bcl-2), TNF α , IL-1 β and vascular endothelial growth factor (VEGF). Results: Daily parenteral challenge with LPS resulted in a dose-dependent delay in ulcer healing with maximum observed at a dose of 5 mg/kg (12.14 ± 1.2 mm2 versus 5.18 ± 0.8 mm2 in the control group). The impairment of ulcer healing in LPS-treated rats was associated with a significant decrease in GBF, increased mRNA expression for IL-1 β , TNF α , the rise in plasma IL-1 β and TNF α levels, an overexpression of COX-2 and VEGF and imbalance in the ratio between pro-apoptotic Bax and antiapoptotic Bcl-2. The daily administration of 50 mg/kg pentoxifylline by itself failed to accelerate the ulcer healing but attenuated the deleterious effects of LPS on this healing. Conclusions: 1) Bacterial endotoxin impairs ulcer healing through the decrease in gastric mucosal blood flow, increased expression and release of proinflammatory cytokines IL-1 β and TNF α , the imbalance between pro- and anti-apoptotic members of Bcl-2 family via downregulation of antiapoptotic bcl-2, and 2) endotoxin leads to upregulation of genes for VEGF and COX-2, which fail to accelerate the ulcer healing.     

胃舒散对乙醇诱导大鼠急性胃损伤的保护作用

目的研究胃舒散对乙醇所致急性胃黏膜损伤（AGML）的保护作用。方法采用乙醇灌胃诱导大鼠AGML模型。采用光镜、扫描电镜和透射观察不同剂量胃舒散（3．0、1．5、0．75g／kg）对黏膜组织形态学的保护作用，并同时检测胃黏膜局部血流量（GMBF）、跨膜电位（PD）、胃组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量和血浆NO水平，等容积的生理盐水和丽珠得乐（1．0g／kg）分别作为正常对照和治疗对照组。结果胃舒散组胃黏膜损伤指数及组织学评分均较模型对照组显著降低（P〈0．05，P〈0．01）；GMBF及PD较模型对照组显著增高（P〈0．0l，P〈0．05）；胃舒散可明显提高胃组织SOD活性（P〈0．05）及血浆NO水平（P〈0．叭）。结论胃舒散对乙醇所致AGML有明显的保护作用，其作用机制可能与增加胃黏膜血流及抗氧化作用有关。     

一氧化氮在雷贝拉唑对大鼠胃黏膜损伤保护中的作用

目的:探讨一氧化氮(NO)在雷贝拉唑对大鼠胃黏膜损伤保护中的作用．方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予雷贝拉唑(20 mg/kg)灌胃,1-硝基-精氨酸甲酯(1-NAME,4 mg／kg)、1-精氨酸(250 mg／kg)及d-精氨酸(250 mg／kg)iv．采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2／NO-3含量,并观察胃黏膜损伤指数(UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化．结果:与模型损伤组比,雷贝拉唑组大鼠UI明显降低(5．5±0．5 vs 25．2±2.3,P<0．01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(坏死物质 → ／≤ :1／9 vs 8／2,P<0．01;中性粒细胞 → ／≤ :3／7 vs 9／1,P<0．01)．预先用1-NAME处理后,雷贝拉唑保护胃黏膜损伤作用明显减弱;1-NAME抑制作用可被1-精氨酸拮抗,而不被d-精氨酸拮抗．向胃内灌注雷贝拉唑,可增加GMBF、胃黏膜和血浆NO-2／NO-3,1-NAME可逆转这种作用,但对雷贝拉唑抑制酸分泌作用无明显影响．结论:雷贝拉唑对大鼠胃黏膜损伤保护作用与NO有关,而与雷贝拉唑抑制酸分泌作用无关．     

十二指肠胃反流对胃黏膜损害的实验性研究

目的：拟通过大鼠实验模型探讨短期十二指肠胃反流(DGR)对胃黏膜的损害及其特点。方法：健康、雄性SD大鼠分成3组：DGR组、结扎幽门组和对照组。手术后3周处死大鼠,观察胃黏膜损害及病理组织学改变、检测胃液pH值、胆红素水平及血清胃泌素水平,透射电镜下观察胃窦黏膜细胞间的紧密连接,测定组织过氧化物酶(MPO)活性。结果：DGR组大鼠胃黏膜可见散在糜烂、溃疡及出血点,而结扎幽门组及对照组胃黏膜光滑。DGR组胃液pH值和胆红素水平明显高于结扎幽门组及对照组,但血清胃泌素水平未见显著升高。短期DGR可引起胃窦黏膜胃小凹增生,没有肠上皮化生及胃黏膜萎缩等。短期DGR炎性细胞浸润不明显,没有导致组织MPO的水平改变,可引起黏膜细胞间的紧密连接受损。结论：DGR短期内可造成胃黏膜损害,表现为胃小凹增生、细胞间紧密连接受损,但炎性细胞浸润不明显,也不引起MPO活性的变化。     

L-精氨酸对糖尿病大鼠睾丸损伤的保护作用

目的 研究L-精氨酸(L-Arg)对糖尿病大鼠睾丸损伤的保护作用及其机制. 方法 电镜下观察L-Arg对STZ诱导的糖尿病大鼠睾丸的形态学改变,并测定睾丸NO、环磷酸鸟苷(cGMP)、内皮素-1(ET-1)、降钙素基因相关肽(CGRP)、丙二醛(MDA)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、SOD、Ca~(2+)-ATPase、Na~+-K~+-ATPase活性,RT-PCR检测睾丸内皮型一氧化氮合酶(eNOS)、iNOS、醛糖还原酶(AR)、CGRP及ET-1 mRNA表达.结果糖尿病组大鼠睾丸电镜下主要见到支持细胞胞质内出现较多空泡,并有大量脂滴沉积,与生精细胞接触处出现空泡;NO、cGMP、CGRP含量及NOS、SOD、Ca~(2+)-ATPase、Na~+-K~+-ATPase活性、CGRP、eNOS mRNA表达均明显低于正常对照组(NC组)(P＜0.05或P＜0.01),而ET-1、MDA含量及AR、ET-1 mRNA表达明显高于NC组(P＜0.01).经L-Arg治疗后,上述改变逆转,与模型组比较,差异有统计学意义(P＜0.05或P＜0.01),电镜下睾丸组织的形态结构接近于NC组. 结论 L-Arg对糖尿病所致的睾丸损伤有一定的保护作用,其机制可能与改善睾丸血供及减轻氧化应激损伤有关.