雌激素对Wistar大鼠实验性变态反应性脑脊髓炎的治疗作用

目的探讨雌激素对大鼠实验性变态反应性脑脊髓炎（EAE）的治疗作用。方法去卵巢模型组采用豚鼠髓鞘蛋白和完全福氏佐剂诱发去卵巢大鼠；治疗组在去卵巢模型组的基础上予以不同剂量雌激素观察各组的发病情况；HE染色观察病理变化。结果低剂量组EAE临床症状较去卵巢模型组轻；高剂量组未出现临床症状；脑和脊髓炎症细胞浸润明显减少。结论雌激素对EAE有治疗作用并与剂量相关。     

雷公藤内酯醇对EAE大鼠外周血CD4+、CD8+的影响

目的探讨雷公藤内酯醇（Tri）对急性实验性变态反应性脑脊髓炎（EAE）大鼠外周血CD4^＋、CD8^＋的影响。方法模型组采用豚鼠髓鞘蛋白和福氏完全佐剂诱发大鼠EAE;治疗组在模型组的基础上予以不同剂量Tri,观察各组的发病情况;流式细胞仪检测外周血CD4^＋、CD8^＋;HE染色和Loyez氏髓鞘染色分别观察病理和髓鞘改变。结果高剂量Tri组未出现临床症状,与模型组和低剂量Tri组比较,高剂量Tri组CD8^＋明显增高、CD4^＋／CD8^＋值明显降低（P〈0．05,〈0．05）;脑和脊髓炎症细胞浸润明显减少;髓鞘结构完整。结论Tri对EAE的治疗有剂量相关性,其作用机制与其增加CD8^＋、降低CD4^＋／CD8^＋值,从而调节机体免疫平衡有关。     

大鼠实验性脑出血后血脑屏障通透性与水通道蛋白4的关系及水蛭素的作用研究

目的研究大鼠脑出血后血脑屏障(BBB)通透性与水通道蛋白4(AQP4)的关系及水蛭素的干预作用。方法采用自体动脉血注入尾状核法制成大鼠脑出血模型,RT-PCR法观察AQP4mRNA的表达,伊文思兰法测量BBB通透性,干湿重法计算脑含水量表示脑水肿。结果与对照组相比,脑出血组及水蛭素组BBB通透性均在出血后6h开始升高〔(0·5955±0·0956)和(0·3594±0·0712)〕,1~3d最高〔(0·8889±0·0968)、(0·7914±0·0520)和(0·5937±0·0505)、(0·5275±0·0492)〕,水蛭素组明显低于脑出血组(P<0·05);两组AQP4mRNA表达也于6h即开始升高〔(1·06±0·12)和(0·83±0·08)〕,3d时达到高峰〔(1·34±0·14)和(1·03±0·05)〕,水蛭素组明显低于脑出血组(P<0·05);BBB通透性与AQP4mRNA表达呈显著正相关(R=0·686,P<0·01),与脑水肿变化趋势一致。结论脑出血后产生的凝血酶可能通过上调APQ4mRNA表达,增加BBB通透性,参与脑水肿形成和发展;水蛭素可抑制此过程。     

α-硫辛酸对EAE大鼠的保护作用和机制探讨

目的研究α-硫辛酸(alpha-lipoic acid,ALA)在实验性变态反应性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠模型中对脊髓组织的保护作用并探讨其机制。方法 Wistar大鼠随机分为对照组(NC组)、EAE组(EAE组)和α-硫辛酸组(ALA组)。对照组不接受任何处理,EAE组接受免疫注射,ALA组在EAE组基础上加用ALA治疗。采用Kono评分法进行大鼠神经功能评估,在实验60 d时取材,观察脊髓腰膨大段组织的病理学改变,以免疫组化方法标记白介素-17(IL-17),观察其表达变化,分光光度计检测脑组织中还原型谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)的含量。结果 EAE组出现明显的神经功能障碍,ALA组大鼠神经功能明显改善(P0.05);免疫细胞化学染色结果显示,EAE组大鼠脊髓腰膨大炎症标记物IL-17蛋白的表达比NC组明显增加(P0.05);ALA治疗后IL-17蛋白的表达显著降低(P0.05);与NC组相比,EAE组大鼠脑组织中GSH含量明显下降(P0.05),MDA含量明显增加(P0.05),ALA治疗后显著增加了GSH含量(P0.05),降低了MDA含量(P0.05)。结论 ALA可能是通过抑制炎症反应和减轻氧化应激发挥了在EAE大鼠模型中的保护作用。     

阿托伐他汀对老年自身免疫性脑脊髓膜炎大鼠脑白质的保护作用

目的探讨阿托伐他汀对老年自身免疫性脑脊髓膜炎(EAE)大鼠脑白质髓鞘碱性蛋白(MBP)和少突胶质细胞转录因子(OLIG)1蛋白表达的影响。方法取老年Wistar雄性大鼠80只,随机分为对照组、模型组、阿托伐他汀大剂量组(8 mg/kg组)和阿托伐他汀小剂量组(2 mg/kg组),每组20只。采用新鲜豚鼠50%全脊髓匀浆液和完全弗氏佐剂(CFA)免疫制备EAE模型,免疫后第2天开始,模型组给予生理盐水灌胃,阿托伐他汀组给予阿托伐他汀不同剂量灌胃,持续灌胃21 d,于第22天处死,取脑干和脊髓待测。采用实时荧光定量和免疫组织化学染色检测各组脑干、脊髓中MBP和OLIG1的mRNA水平和蛋白阳性表达强度。结果与对照组比较,模型组MBP mRNA水平和蛋白阳性表达强度明显升高、OLIG1明显降低(P0.01);阿托伐他汀小剂量组MBP mRNA水平和蛋白阳性表达强度升高、OLIG1降低(P0.01);阿托伐他汀大剂量组MBP mRNA水平和蛋白阳性表达强度略升高、OLIG1略降低,无显著差异(P0.05),模型组、阿托伐他汀大、小剂量组差异显著(P0.01)。结论阿托伐他汀能够通过下调MBP、上调OLIG1 mRNA水平和蛋白阳性表达强度,对EAE大鼠的脑白质髓鞘损伤具有保护作用,且大剂量作用优于小剂量。     

神经生长因子对糖尿病大鼠坐骨神经形态学的影响

目的 研究神经生长因子(NGF)对糖尿病大鼠周围神经病变的影响。方法 糖尿病大鼠造模后2周开始连续后肢肌注 NGF(800 U·kg~(-1)·d~(-1)),应用甲苯胺蓝染色及透射电镜观察大鼠坐骨神经的形态学变化。结果 糖尿病造模后2周电镜下坐骨神经即出现葱管样改变,且该病理改变随时间加重,6个月出现脱髓鞘。3个月及6个月NGF治疗组(NGF组)大鼠坐骨神经的神经纤维髓鞘及轴突面积较相应的糖尿病组(DM组)均增加,3个月NGF组及DM组坐骨神经纤维髓鞘面积分别为(47.48±11.84)μm~2和(44.86±12.28)μm~2(P<0.05);6个月分别为(57.76±10.33)μm~2和(46.34±11.57)μm~2(P<0.05)。3个月NGF组及DM组坐骨神经纤维的轴突面积分别为(22.86±9.59)μm~2和(19.86±7.78)μm~2(P<0.05);6个月分别为(23.90±7.18)μm~2和(20.29±6.67)μm(P<0.05)。6个月NGF组较3个月组髓鞘面积增加,并可减少坐骨神经纤维脱髓鞘。结论 早期、长期应用NGF可以有效改善糖尿病大鼠周围神经病变的形态。     

左归丸与右归丸对EAE大鼠APP及GAP-43表达的影响

目的 观察左归丸和右归丸对实验性变态反应性脑脊髓炎(EAE)大鼠淀粉样前体蛋白(APP)及生长相关蛋白[GAP-43)表达的影响,探讨滋阴与温阳补肾法治疗EAE的可能机制.方法 应用髓鞘碱性蛋白(MBP)68-86免疫诱导Lewis大鼠建立EAE模型.免疫后第7天、第14天、第28天取大鼠脑白质与脊髓,采用Western-blot和实时荧光定量RT-PCR技术检测APP及GAP-43蛋白及mRNA的表达.结果 免疫后第7天,激素和左归丸均能升高EAE大鼠脊髓中APP和脑白质中APP mRNA的过低表达(P<0.05或P<0.01),且在脊髓中二者对APP的调节优于右归丸(P<0.05);第14天,左归丸显著调节脑白质中APP mRNA的过高表达、脊髓中APP mRNA的过低表达(P<0.05或P<0.01),作用优于右归丸(P<0.05).免疫后第7天,激素与左归丸显著上调EAE大鼠脑白质和脊髓中GAP-43水平(P<0.05或P<0.01),在脊髓中二者作用优于右归丸(P<0.01),右归丸显著下调脑白质中GAP-43 mRNA的表达(P<0.05);第14天,激素与左归丸显著抑制脑白质中GAP-43的过高表达(P<0.05);第28天,激素组与左归丸组脑白质中GAP-43水平低于模型组与右归丸组(P<0.01).结论 左右归丸对EAE大鼠脑白质和脊髓中APP和GAP-43蛋白与基因的表达均具有一定调节作用,且左归丸的作用明显优于右归丸.     

早期肠道营养对烧伤大鼠肠粘膜损伤和修复的影响

目的研究早期肠道营养对烧伤大鼠肠粘膜损伤和修复的影响及其可能的机制.方法采用30%体表面积Ⅲ度烧伤大鼠模型,随机分成伤前对照(C),静脉营养(PN)及肠道营养(EN)组,EN和PN组给予等氮、等热卡、等体积的营养液.在此基础上动态观察了肠组织中肠三叶因子(ITF)含量、血浆二氨氧化酶(DAO)活性、肠粘膜跨膜电位差(PD)及增殖细胞核抗原(PCNA)的变化,并进行相关分析.结果烧伤后肠粘膜组织结构受损,血浆DAO活性明显增高,从伤前的0.32±0.02(103U·L-1)增为1.23±0.53(103U·L-1),相差显著(P＜0.01).而PD,PCNA值及ITF含量分别从伤前的13.53±0.41(mV),823.46±240.56(A),369±65(ng·g-1)降至伤后的5.27±0.17(mV),247.39±112.23(A)和15±4(ng·g-1),相差显著(P＜0.05～0.01).两组相比EN组大鼠肠道受损程度明显低于PN组,同时其ITF含量、PD,PCNA值均高于PN组[EN组分别为129±46(ng·g-1),6.02±0.17(mV)和612.66±188.27(A)而PN组分别为15±4(ng·g-1),5.27±0.17(mV)和247.39±112.23(A)];而EN组大鼠血浆DAO活性为0.61±0.14(103U·L-1)显著低于PN组的0.90±0.16(103U·L-1)(P＜0.01).相关分析显示,ITF含量同血浆DAO活性呈显著负相关(r1=-0.964,P＜0.01),而同PCNA及PD值呈显著正相关(r2=0.884,P＜0.05;r3=0.983,P＜0.01).结论严重烧伤后肠粘膜结构受损与肠道合成和分泌ITF的能力大幅下降有关,肠道营养可降低伤后ITF下降的幅度可能是其在减轻肠粘膜损伤,促进肠粘膜修复方面优于静脉营养的重要原因.     

骨髓间充质干细胞移植对自身免疫性脑脊髓炎大鼠神经功能和病理改变的影响

目的探讨骨髓间充质干细胞（BMSCs）移植对自身免疫性脑脊髓炎（EAE）大鼠神经功能及脑组织病理改变的影响。方法以豚鼠全脊髓匀浆和完全弗氏佐剂为抗原免疫Wistar大鼠,制备EAE模型。将造模成功大鼠随机分为EAE模型组、假性治疗组及BMSCs治疗组。BMSCs治疗组在发病第1天应用立体定向侧脑室注射的方法将体外培养的BMSCs（1×106个）移植到EAE大鼠体内。每日观察记录神经功能评分,移植后14 d处死大鼠,应用HE染色及Bielschowsky银染观察脑组织病理变化。结果与EAE模型组及假性治疗组相比,BMSCs治疗组的神经功能评分明显降低（P〈0.05）。脑组织病理学观察显示,在EAE急性期,脑白质区有大量炎性细胞浸润,在血管周围形成袖套样结构,并可见轴突损伤。BMSCs治疗组病变程度和范围明显减轻。结论 BMSCs能改善EAE大鼠的症状,减轻脑组织的病理损害。     

罗格列酮对大鼠动脉粥样硬化斑块形成的影响

目的探讨罗格列酮对大鼠动脉粥样硬化(AS)斑块的作用及可能机制。方法12周龄雄性Wistar大鼠55只,随机分为对照组20只、模型组20只、治疗组15只。对照组大鼠喂食基础饲料;模型组和治疗组在喂食开始时一次性腹腔注射维生素D_3 40万IU/kg,喂食高脂饲料。6周后,处死对照组和模型组大鼠各5只,提取全长主动脉,油红O染色进行病变分级评分;HE染色观察斑块的病理形态改变;免疫组化法测定过氧化物酶体增殖物激活受体γ(PPARγ)蛋白表达;并测空腹血糖、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。剩余大鼠继续喂养至12周,模型组和治疗组同时分别给予生理盐水(10 m1·kg~(-1)·d~(-1))和罗格列酮(3 mg·kg~(-1)·d~(-1))灌胃治疗。6周后,各组大鼠处死后按前述方法再次检测各指标。结果造模6周后,模型组大鼠空腹血糖、FINS、HOMA-IR升高(P＜0．05);主动脉病变评分明显增高(P＜0．01);光镜下可见典型的AS斑块;免疫组化染色显示PPARγ蛋白平均吸光度值明显增强(P＜0．01)。治疗6周后,治疗组与模型组比较,空腹血糖[(5．28±1．44)mmol/L和(8．90±2．60)mmol/L]、FISN[(31．04±24．20)mU/L和(48．38±27．62)mU/L]及HOMA-IR[(7．78±2．61)mmol/L和(12．42±4．13)mmol/L]水平降低(P＜0．05或P＜0．01),但与对照组[(6．01±0．89)mmol/L、(32．15±25．28)mU/L、7．79±2．58]比较,差异无统计学意义;治疗组主动脉斑块评分明显低于模型组(P＜0．01),但略高于对照组(P＜0．05)。光镜下可见治疗组AS病变较模型组明显减轻,且PPARγ蛋白平均吸光度值降低(P＜0．01)。结论罗格列酮治疗6周后,大鼠AS斑块明显消退,激活PPARγ和改善胰岛素抵抗可能是其作用机制之一。     

Differential suppression of experimental allergic diseases in rats infected with trypanosomes

PVG/c rats, infected 3 days previously with 10(3) Trypanosoma brucei brucei S.42 organisms failed to develop adjuvant disease in response to an intradermal inoculation of mycobacterial adjuvant. By contrast, similarly infected rats, immunized with heterologous brain and spinal cord in Freund's complete adjuvant with pertussis vaccine as a secondary adjuvant, developed clinical signs of allergic encephalomyelitis (EAE) at least as severe as those in uninfected rats. Delayed hypersensitivity reactions to PPD were depressed in trypanosome-infected, adjuvant-injected rats, as were the reactions to myelin basic protein in infected rats developing EAE. There appeared to be no cross-reactivity between trypanosomal antigen and myelin basic protein which could account for the lack of suppression of EAE. It is suggested that the different extent to which autoimmunity is involved in these two experimental allergic diseases may account for the differential suppressive activity of trypanosome infections upon them.     

Susceptibility and resistance to experimental allergic encephalomyelitis: relationship with hypothalamic-pituitary-adrenocortical axis responsiveness in the rat.

Susceptibility to experimental allergic encephalomyelitis (EAE) may be influenced by variations in the production of endogenous glucocorticoids. We investigated whether this concept is consistent across different genotypes and paradigms of EAE. In the major histocompatibility complex-disparate rat strains, Lewis (LEW), Brown Norway (BN), and Dark Agouti (DA), inflammatory and inflammatory-demyelinating variants of EAE were induced by immunization with myelin basic protein and myelin oligodendrocyte glycoprotein, respectively. We analyzed hormone production in EAE and after exposure to novel environment. DA and BN rats showed a robust hypothalamic-pituitary-adrenocortical (HPA) axis response to novelty stress and produced significantly higher ACTH and corticosterone plasma levels compared with LEW rats. However, HPA axis responsiveness was not associated with a generalized resistance to EAE, as both DA and LEW rats were susceptible to myelin basic protein-induced EAE. Moreover, both robust HPA responder strains, DA and the EAE-resistant BN rat, were highly susceptible to myelin oligodendrocyte glycoprotein-induced EAE. In animals of all strains, clinical disease was associated with significantly elevated plasma levels of corticosterone, and no differences in brain glucocorticoid-binding receptors were detected. Therefore, HPA axis characteristics are not a predictor of disease susceptibility in EAE.     

Neurointermediate pituitary lobectomy decreases the incidence and severity of experimental autoimmune encephalomyelitis in Lewis rats

Acute experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system, mediated by T lymphocytes. Immunization of Lewis rats with myelin antigens suspended in complete Freund's adjuvant induces EAE. In a previous study on rats we have found that neurointermediate pituitary lobectomy (NIL) decreased both the humoral and cell-mediated immune responses. Here we investigated the effect of NIL on the incidence and severity of EAE and on the function of the hypothalamic-pituitary-adrenal axis in Lewis rats. NIL, hypophysectomized (Hypox) and sham-operated (Sham) rats were immunized s.c. with guinea-pig brain extract suspended in complete Freund's adjuvant. Untreated rats were used as controls. Water intake, body weight gain, clinical and histopathologic incidence and severity of EAE were evaluated in the operated groups. On killing, plasma adrenocorticotropin and corticosterone levels were measured and adrenals, thymuses and spleens were weighed. Histopathologic lesions were counted in the brain and spinal cord. Water intake and body weight gain were significantly decreased in Sham and Hypox animals with EAE whereas higher intakes persisted in the NIL group. Plasma levels of adrenocorticotropin were within the normal range whereas corticosterone levels increased in Sham and occasionally in NIL animals. Thymus weights were decreased in NIL and Hypox groups. The clinical and histopathologic incidence and severity of EAE were significantly decreased in NIL animals as compared with Sham and Hypox rats. We concluded that NIL affects the cell-mediated immune response and plays a role in the development and progression of EAE in the Lewis rat.     

Antibodies to CD44 and integrin α4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment

The role of various adhesion molecules in lymphocyte homing to the brain and in inflammatory autoimmune disease of the central nervous system (CNS) was examined in mice. Activated T cell lines and clones expressed CD44 and integrin alpha4, but not L-selectin, and entered the CNS independent of their antigen specificity. mAbs directed against CD44 and integrin alpha4 prevented the transfer of experimental autoimmune encephalomyelitis (EAE) by myelin basic protein-specific T cells. T cells preincubated with anti-CD44 or antiintegrin alpha4 were blocked only partially from entering the brain parenchyma. However, both antibodies efficiently prevented CNS inflammation and clinical expression of EAE when injected in vivo. This effect lasted as long as antibodies were administered. Antibodies specific for L-selectin had no effect on homing of encephalitogenic T cells to the brain or development of EAE. Antiintegrin alpha4 and anti-CD44 did not impair the activation and function of encephalitogenic T cells in vitro and did not deplete integrin alpha4- or CD44-positive cells in vivo. These data suggest that, in the absence of leukocyte recruitment, the entry of a reduced number of activated myelin basic protein-reactive T cells in the CNS is not sufficient for the development and expression of EAE. We propose that antibodies to integrin alpha4 and CD44 prevent clinical disease by partially targeting the primary influx of encephalitogenic T cells and by preventing the secondary influx of leukocytes to lesions initiated by the transferred T cells.     

空肠弯曲菌脂多糖对大鼠脊髓髓鞘损伤的实验研究

目的 探讨空肠弯曲菌脂多糖(Cj-LPS)对大鼠脊髓髓鞘损伤的影响。方法 Wistar大鼠分为对照组(NC组)、脂多糖组(Cj-LPS组)和抗LPS组(Anti-LPS组)。NC组使用试剂为生理盐水混合完全弗氏佐剂(CFA);Cj-LPS组试剂则由Cj-LPS、CFA和生理盐水组成;抗LPS组试剂为特异性抗Cj-LPS IgG混合CFA。注射后第4周和第6周分别处死各组大鼠。光镜观察脊髓组织形态变化,RT-PCR检测神经营养因子-3(NT-3)及其受体TrkC和神经生长抑制因子NogoA及其受体NgR mRNA的表达。结果 Cj-LPS组大鼠出现脊髓髓鞘损伤, NT-3/TrkC mRNA的表达下降, NogoA/NgR mRNA的表达增加;与Cj-LPS组比较,抗LPS组脊髓髓鞘损伤减轻。结论 Cj-LPS可诱导大鼠脊髓髓鞘损伤,而抗LPS抗体可以改善由Cj-LPS诱导的大鼠脊髓髓鞘损伤。     

高氟对大鼠甲状腺功能和脑损伤的影响

目的 观察高氟对大鼠甲状腺功能和脑损伤的影响.方法 将36只成年Wistar大鼠按性别和体质量随机分为3组:对照组、高氟组、高氟+甲状腺片组,每组12只,分别饮用自来水(含氟量<5 mg/L),加入100、100 ms/L氟化钠(NaF)的自来水:喂养7个月后高氟+甲状腺片组大鼠另给予0.04%甲状腺片(1.8ml·kg~(-1)·d~(-1))灌胃3周.喂养7个月零3周时,用放射免疫法测定各组大鼠血清TT_3、TT_4;光镜下观察大鼠甲状腺和脑组织形态结构;免疫组化方法检测海马区域NMDAR2B蛋白表达.结果 与对照组[(0.97±0.15)、(84.03±12.45)nmol/L]比较,高氟组大鼠血清TT_3、TT_4明显降低[(0.24 ±0.07)、(15.16±2.08)nmoL/L,P均<0.01];高氟+甲状腺片组与对照组比较,未见明显改变[(1.02 ±0.19)、(85.63±9.55)nmoL/L,P均>0.05],与高氟组相比较,明显增高(P均<0.01).光镜下高氟组可见甲状腺部分滤泡上皮增生、排列紊乱、萎缩,滤泡腔内胶质减少,而高氟+甲状腺片组与高氟组比较,甲状腺滤泡上皮增生程度减轻;高氟组海马神经元细胞肿胀、排列紊乱,高氟+甲状腺片组海马神经元细胞较高氟组肿胀减轻、排列有序.高氟组海马CA1、CA3区NMDAR2B阳性细胞灰度值(167.05±7.31)较对照组(92.53±9.67)和高氟+甲状腺片组(101.66±12.21)明显增高(P均<0.01).结论 高氟可导致成年大鼠甲状腺功能降低、形态改变,并引起大脑病理损害;在高氟损伤基础上给予甲状腺制剂替代后,大鼠甲状腺功能和形态可基本恢复正常,脑组织损伤明显减轻.慢性氟中毒造成的甲状腺功能降低可能是高氟造成脑损伤的另一重要参与因素.     

Immunohistochemical localization and mRNA expression of apolipoprotein A-I in rat spinal cord

Apolipoproteins in the cerebrospinal fluid (CSF) play important roles in lipid metabolism in the central nervous system. Although it has been demonstrated that apo E is synthesized in the neuron, the synthesis of apo A-I has only been determined in fish and chicken. It was demonstrated that apo A-I concentrations in the CSF were increased in poliovirus-infected macaques, however, the origin of the CSF apo A-I was not determined. The present immunohistochemical study provided evidence that apo A-I was localized within the nerve cell body of the rat spinal cord. In situ hybridization also showed that apo A-I mRNA was predominantly expressed in the neurons. As a further experiment, we compared apo A-I levels in the spinal cord from control rats and rats with experimental allergic encephalomyelitis (EAE), which was induced by sensitization with myelin basic protein. Although no significant changes in serum apo A-I levels were observed, apo A-I levels in the spinal cord were significantly elevated in EAE rats. Furthermore, apo A-I in the spinal cord of rats with EAE was not seen in the nerve cell body, but at the interstitium, particularly in lesions where inflammation had occurred. The current study clearly demonstrated that apo A-I is synthesized in the neurons of the rat spinal cord and the synthesis was suppressed in EAE rats.     

沙格列汀和格列本脲对2型糖尿病大鼠主动脉内皮细胞核因子κB及血管细胞间黏附因子1表达的影响

目的 观察沙格列汀对T2DM大鼠主动脉内皮细胞核因子κB（NF-κB）、血管细胞间黏附因子1（VCAM-1）表达的影响. 方法 将成模大鼠分为糖尿病对照（DM）组、格列本脲治疗（DMG）组和沙格列汀治疗（DMS）组.DMG、DMS组分别予格列本脲、沙格列汀治疗8周.12周末检测各组FPG、FIns、血脂、NF-κB和VCAM-1表达,计算胰岛素抵抗指数（HOMA-IR）,观察大鼠主动脉形态学变化.结果 12周末,与DMG组比较,DMS组FIns[（11.38±1.56） vs（6.13±0.54） μIU/ml]、TG[（1.17±0.15）vs （0.72±0.25）mmol/L]、LDL-C[（0.57±0.05）vs（6.13±0.54） mmol/L]、HOMA-IR[（12.78±1.53）vs（6.78±0.57）]、NF-κB平均灰度值[（143.33±13.38）vs（121.67±11.43）]和VCAM-1平均灰度值[（153.33±12.74）vs（133.00±11.53）]表达降低（P＜0.05）. 结论 沙格列汀在改善糖、脂代谢的同时,可下调糖尿病大鼠主动脉内皮升高的NF-κB、VCAM-1蛋白表达量,可能参与改善大血管并发症.     

福辛普利对自发性高血压大鼠脑超微结构及Klotho基因表达的影响

目的 观察药物干预后高血压脑损害的超微结构及其脑组织中Klotho基因和微炎症因子--血管细胞粘附分子1和细胞间粘附分子1的表达状况.方法 选取22周龄雄性自发性高血压模型鼠10只,随机分为高血压组与福辛普利干预组(5只/组),Wistar-kyoto大鼠(WKY)5只作为正常对照组.通过电镜观察各组大鼠脑的超微结构,通过RT-PCR检测、免疫组织化学技术和western印迹检测Klotho基因和微炎症因子血管细胞粘附分子1和细胞间粘附分子1的表达状况.结果 高血压损害脑神经元的结构、主要表现为细胞固缩、染色质边集、典型凋亡小体形成,但经过福辛普利干预后,其神经元损害有所减轻.RT-PCR结果显示福辛普利干预能够上调Klotho基因mRNA表达(P<0.05)、下调微炎症因子血管细胞粘附分子1和细胞间粘附分子1mRNA的表达(P<0.01);免疫组织化学技术和Western-blot检测证实福辛普利干预能够增加Klotho蛋白的表达,同时减血管细胞粘附分子1和细胞间粘附分子1蛋白的表达.结论 福辛普利能够上调Klotho的表达,改善高血压脑超微结构的改变.     

Brain endothelial adhesion molecule expression in experimental colitis

OBJECTIVES: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. METHODS: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified, using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SCID mice reconstituted with CD45RBhigh T-cells, and in IL-10-/- mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD45 monoclonal antibody. RESULTS: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RBhigh transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. CONCLUSIONS: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not associated with an infiltration of leukocytes into brain tissue.