Exendin-4对糖尿病小鼠胰腺survivin表达的影响

目的观察exendin-4(Ex)对链脲佐菌素(STZ)诱导的糖尿病小鼠模型胰腺survivin基因表达的影响,旨在探讨ex-endin-4抗凋亡作用的机制。方法6 wk ♂ BALB/c小鼠分为3组:STZ组、Ex组(STZ+Ex)、对照组。每周测量血糖,4wk时胰腺行免疫组化、TUNEL检测,实时荧光RT-PCR方法检测胰腺survivin表达水平。结果Ex组血糖低于STZ组,胰岛中胰岛素染色阳性面积百分比大于STZ组(39.40±9.72vs25.47±9.26,P<0.01),胰岛凋亡细胞数目少于STZ组。STZ注射后第4周胰腺survivin mRNA水平升高,Ex组更高,差异有统计学意义(P<0.05)。结论Ex可抑制STZ诱导糖尿病小鼠的胰岛细胞凋亡,此作用可能部分通过上调胰腺survivin表达介导。     

玉竹提取物A对1型糖尿病小鼠血糖及细胞因子的调控作用

目的:研究1型糖尿病(DM)的发生与细胞因子作用的关系及玉竹提取物A(EA-PAOA)对链脲佐菌素(STZ)诱导的1型糖尿病小鼠(下称STZ小鼠)血糖和细胞因子的影响。方法:昆明小鼠60只,对EA-PAOA进行急性毒性实验。采用STZ小剂量多次注射诱导1型糖尿病小鼠模型,正常对照组与DM对照组各1组,实验组分三个剂量腹腔注射等体积EA-PAOA,用药4周监测血糖变化,4周后应用EL ISA法检测外周血血清IL-4、IL-10、IFN-γ含量。结果:急性毒性实验显示EA-PAOA毒性作用很低,LD 50=14.5124g/K g;DM对照组与正常对照组比较IL-4、IL-10降低,IFN-γ升高;实验组与DM对照组比较血糖明显降低,IL-4、IL-10升高,IFN-γ降低。结论:1型DM的发生与细胞因子IL-4、IL-10降低,IFN-γ升高有关,EA-PAOA安全范围大,可调节STZ小鼠发病过程中细胞因子水平,干预1型DM发生发展。     

体内应用编码人白介素-10质粒DNA对实验性自身免疫性甲状腺炎小鼠的基因治疗(英文)

目的:研究白介素-10(IL-10)对实验性自身免疫性甲状腺炎小鼠的基因治疗作用。方法:将IL-10质粒DNA注射入由猪甲状腺球蛋白(pTg)诱发的自身免疫性甲状腺炎小鼠甲状腺内,pTg免疫后28天,进行甲状腺IL-10 mRNA表达和组织学等检查。结果:IL-10质粒DNA注射后1周或2周甲状腺均有IL-10 mRNA表达;转染IL-10质粒DNA的COS-7细胞48小时有显著IL-10 mRNA表达,同时转染后48、72小时细胞培养液中IL-10浓度显著增高;治疗组小鼠甲状腺淋巴细胞浸润指数(1.1±0.4)明显低于对照组(2.2±0.5)(P<0.01);治疗组小鼠血清IFN-Υ水平明显低于对照组(P<0.01)。结论:甲状腺直接注射编码IL-10质粒DNA能显著抑制自身免疫性甲状腺炎淋巴细胞对甲状腺的浸润,缓解病情的发展。     

胰岛新生相关蛋白对链脲佐菌素诱导的糖尿病小鼠的治疗作用

目的 观察腹腔注射胰岛新生相关蛋白(INGAP)对链脲佐菌素(STZ)诱导的糖尿病(DM)小鼠的治疗作用.方法 C57BL/6小鼠腹腔注射STZ建立DM模型,将成模后小鼠随机分为INGAP组和磷酸盐缓冲液(PBS)对照组.INGAP组每日给予腹腔注射INGAP 500 μg;对照组注射等体积PBS.两组均隔日监测血糖至第34天,用实时荧光定量-PCR检测小鼠胰腺中葡萄糖转运蛋白-2(Glut-2)和胰腺十二指肠同源盒1(PDX-1)mRNA的表达.结果 INGAP组血糖未见明显下降;但与对照组比较,INGAP可以使DM小鼠胰腺中PDX-1、Glut-2 mRNA的表达增加(P＜0.05).结论 腹腔注射INGAP不能使STZ诱导的DM小鼠血糖下降,但能够使胰腺中的PDX-1、Glut-2表达最提高.     

强直性脊柱炎外周血Th17细胞的检测及意义

目的 探讨Th17细胞在强直性脊柱炎(AS)患者外周血中的水平及意义.方法 取40例AS患者(分AS病情稳定组、活动组各20例)和健康人外周血单个核细胞(PBMC),免疫磁珠阴选CD4~+ T细胞,用或不用非特异性刺激剂(A-CD3、A-CD28),然后加PMA/Ion,经固定/透膜处理进行细胞内染色,流式细胞术(FCM)检测CD4~+T细胞内白细胞介素17(IL-17~+)/γ于扰素(IFN-γ~+)、IL-17~+/IL-6~+水平.结果 免疫磁珠阴选CD4~+T细胞纯度达90% 以上.AS病情活动组IL-17表达水平较病情稳定组和健康对照组显著增高(P<0.01).用A-CD3、A-CD28和IL-23刺激后,CD4~+ T细胞IL-17胞内表达水平较无刺激有一定的增加.AS患者CD4~+T细胞IFN-γ胞内表达水平呈现卜IL-17表达相似的特点.AS患者IL-17胞内表达水平与IFN-γ和IL-6无显著相关.结论 AS患者外周血CD4~+ T细胞胞内IL-17和IFN-γ高表达,提示分泌IL-17的Th17细胞和分泌IFN-γ的Th1细胞共同参与了AS发病过程.     

1,25(OH)_2D_3对NOD小鼠1型糖尿病的免疫干预及其机制研究

目的观察1,25(OH)2D3对雌性非肥胖糖尿病(NOD)小鼠糖尿病发病率、胰岛炎的影响,以及外周免疫器官脾脏T淋巴细胞亚群的变化,血清细胞因子干扰素γ(IFN-γ)、白细胞介素-4(IL-4)及一氧化氮(NO)的水平,从而更好地揭示1,25(OH)2D3的免疫调节机制。方法离乳(21 d龄)的雌性NOD小鼠(80只)随机分为两组:第1组给予1,25(OH)2D3(5μg/kg)隔日1次腹腔注射,共7周,作为实验组。第2组给予等量花生油作为对照组(40只),给药时间、方法同前。10周龄时腹腔注射环磷酰胺以加速糖尿病。加速1周后各取15只通过酶联免疫吸附试验(ELISA)法检测IFN-γI、L-4水平,生化比色法检测NO水平,流式细胞仪分析脾组织T细胞亚群的变化。其余继续观察。小鼠在被确诊糖尿病或环磷酰胺加速后1个月处死,观察胰腺病理变化、糖尿病发病率及血钙水平。结果实验组发病率(12%)明显低于对照组(56%),P<0.01;实验组胰岛炎症分数较对照组明显降低P<0.01,炎症程度也明显减轻;实验组血清IL-4较对照组明显升高[(52±9)ng/Lvs(33±3)ng/L],P<0.01;IFN-γ、NO较对照组显著降低[(71±16)ng/Lvs(141±11)ng/L,(78±28)ng/Lvs(118±19)ng/L],P均<0.01;脾脏淋巴细胞经流式细胞仪测定,结果显示实验组T细胞CD4+、CD8+亚群较对照组显著升高,CD4+亚群为47±6与35±4(P<0.01),CD8+亚群为11.6±3.6与7.8±1.5(P<0.05),而CD4+/CD8+亚群分别为4.3±0.9与4.6±0.9(P>0.05),两组差异无统计学意义;实验组血钙较对照组稍高,但NOD小鼠可以很好耐受。结论1,25(OH)2D3可以预防环磷酰胺加速的NOD小鼠糖尿病的发生,并可减轻胰岛炎。其机制:①可能与增加Th2型细胞因子的全身表达,降低Th1型细胞因子的全身表达,从而调节Th1/Th2型细胞因子比例失衡有关。②可能与增加抑制性T细胞数目,促进CD4+T细胞由Th1向Th2亚群转化有关。该实验同时证实了NO在糖尿病的发生机制中起一定作用。     

柠檬苦素对MFC胃癌荷瘤模型小鼠免疫功能及凋亡相关因子表达的影响

目的:研究柠檬苦素对MFC胃癌荷瘤模型小鼠免疫功能及凋亡相关因子表达的影响。方法:将MFC胃癌细胞接种于小鼠右侧腋下以复制MFC胃癌荷瘤模型,造模成功后分为模型组、环磷酰胺组(阳性对照,25 mg/kg)和柠檬苦素高、中、低剂量组(100、50、25 mg/kg),每组10只。除模型组小鼠灌胃0.5%羧甲基纤维素钠外,其余各组小鼠灌胃相应药物,每天1次,连续14天。小鼠给药前及末次给药后均测定体质量,并在末次给药后取脾、胸腺、肿瘤组织以计算脾指数、胸腺指数及抑瘤率;采用流式细胞术检测小鼠CD4⁺、CD8⁺T淋巴细胞百分数和CD4⁺/CD8⁺比值;采用酶联免疫吸附法检测小鼠血清中免疫功能相关指标[白细胞介素2(IL-2)、IL-10、干扰素γ(IFN-γ)]的表达水平;采用实时定量聚合酶链式反应法和Western blot法检测小鼠肿瘤组织中凋亡相关因子[细胞色素C(Cyt-C)、B淋巴细胞瘤2蛋白(Bcl-2)、Bcl-2相关X蛋白(Bax)]的mRNA和蛋白的相对表达水平。结果:除环磷酰胺组小鼠体质量较模型组显著降低外(P<0.05),其余各组小鼠体质量的差异均无统计学意义(P<0.05)。环磷酰胺组和柠檬苦素高、中、低剂量组小鼠的抑瘤率分别为(58.16±7.07)%、(37.09±4.26)%、(27.30±3.64)%、(15.13±2.95)%。与模型组比较,环磷酰胺组小鼠脾指数、胸腺指数、CD4⁺和CD8⁺T淋巴细胞百分数、CD4⁺/CD8⁺比值、血清中IL-2和IL-10的表达水平、肿瘤组织中Bcl-2的mRNA和蛋白的相对表达水平以及柠檬苦素各剂量组的IL-10表达水平、Bcl-2的mRNA和蛋白的相对表达水平均显著降低(P<0.05);环磷酰胺组IFN-γ表达水平、Cyt-C和Bax的mRNA和蛋白的相对表达水平,以及柠檬苦素各剂量组的脾指数(低剂量组除外)和胸腺指数、CD4⁺和CD8⁺T淋巴细胞百分数、CD4⁺/CD8⁺比值、IL-2和IFN-γ的表达水平、Cyt-C和Bax的mRNA和蛋白的相对表达水平均显著升高(P<0.05)。结论:柠檬苦素能抑制MFC胃癌荷瘤模型小鼠肿瘤组织的生长,且毒副作用相对较小;其作用机制与提高免疫功能和诱导凋亡有关。     

CpG寡脱氧核苷酸对1型糖尿病患者外周血单个核细胞功能的影响

目的:观察CpG寡脱氧核苷酸(ODN)对1型糖尿病患者与健康志愿者外周血单个核细胞(PBMC)γ干扰素(IFN-γ)、白细胞介素(IL)-12以及IL-10表达的影响。方法:将1型糖尿病患者与健康志愿者的PBMC根据刺激物不同分为对照组、CpG组(CpGODN 2 nmol·mL-1)。用逆转录-聚合酶链反应(RT-PCR)法检测PBM CIFN-γmRNA、IL-12mRNA和IL-10mRNA的表达。结果:1型糖尿病患者IFN-γmRNA和IL-12mRNA的表达明显低于健康志愿者;1型糖尿病患者与健康志愿者PBMC经CpGODN刺激后,IFN-γ mRNA和IL-12mRNA的表达均高于对照组(P<0.01,P<0.01),IL-10mRNA的表达与对照组相似(P>0.05)。结论:1型糖尿病患者PBMC表达IFN-γ和IL-12下降,CpGODN可促进其表达,增强其免疫调节能力。     

慢性乙型肝炎患者细胞毒T细胞内穿孔素、干扰素及白细胞介素10表达与病毒消除的关系

目的对慢性乙型肝炎患者细胞毒T细胞内穿孔素(Perforin)、干扰素(IFN-γ)及白细胞介素10(IL-10)表达与病毒消除的关系进行研究分析,为今后的临床工作提供有价值的参考依据。方法选择2017年1月至2019年6月我院收治的获得临床确诊的慢性乙型肝炎患者56例作为研究对象,定义为观察组,另取同期健康体检者56名作为对照组,对其进行外周血短期培养,采取流式细胞术对CD8+细胞内Perforin、IFN-γ、IL-10的表达水平进行检测,并对两组受试者检测结果进行对比分析。采用荧光定量PCR法对慢性乙型肝炎患者HBV DNA载量进行检测,对病毒载量与CD8+细胞内Perforin、IFN-γ、IL-10表达的关系进行分析。结果观察组患者CD8+细胞内Perforin、IFN-γ、IL-10表达水平较对照组发生显著降低(P <0.05);观察组HBeAg阳性患者CD8+细胞内Perforin、IFN-γ、IL-10表达水平较HBeAg阴性患者发生显著降低(P <0.05);观察组CD8+细胞内Perforin、IFN-γ、IL-10的表达水平与HIV DNA载量呈现明显负相关(P <0.05)。结论慢性乙型肝炎患者细胞毒T细胞内Perforin、IFN-γ、IL-10表达水平会发生显著减少,并且与慢性乙型肝炎患者病毒长期存在有关,与病程迁延不愈存在密切联系,在今后的临床诊断和治疗中,应对其给予足够的关注。     

体外阻断CD137-CD137L途径抑制移植物抗宿主病的免疫效应

目的探讨体外阻断活化的供鼠T淋巴细胞CD137-CD137L共刺激途径抑制供鼠淋巴细胞的免疫反应。方法应用雄性供鼠BALB/c脾淋巴细胞为反应细胞,雌性受鼠C57BL/6脾淋巴细胞为刺激细胞,进行混合淋巴细胞培养(MLC)。设单抗实验组(加抗CD137L单抗)和对照组(不加抗CD137L单抗),初次和再次MLC第1、3、5、7天采用流式细胞术检测CD3+CD4+T细胞、CD3+CD8+T细胞;RT-PCR法检测培养的细胞IL-2、IFN-γ、IL-4、IL-10的水平。结果实验组CD3+CD8+T细胞明显低于对照组(P<0.01);实验组IL-2、IFN-γ水平明显低于对照组(P<0.01);实验组IL-10表达明显高于对照组(P<0.01)。结论体外MLC中,应用抗CD137L单抗孵育供鼠脾T淋巴细胞主要抑制供鼠CD3+CD8+T细胞的增殖,抑制Ⅰ类细胞因子IFN-γ及IL-2的表达,促进Ⅱ类细胞因子IL-10的表达。     

Direct transfer of A20 gene into pancreas protected mice from streptozotocin-induced diabetes

AIM: To investigate the efficiency of transfer of A20 gene into pancreas against STZ-induced diabetes. METHODS:PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20 transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined. RESULTS:Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen,duodenum, and islets. The development of diabetes was prevented by direct A20 gene transferring into the pancreas and A20-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A20-treated mice. CONCLUSION: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A20 gene into the pancreas protected mice from STZ-induced diabetes.     

不同剂量谷氨酸脱羧酶对非肥胖型糖尿病小鼠发生1型糖尿病的影响

目的不同剂量谷氨酸脱羧酶(GAD)对非肥胖型糖尿病小鼠(NOD)糖尿病免疫干预效果的影响。方法将3周龄40只体重(10.0±0.9)g雌性NOD小鼠分为4组分别腹腔注射GAD0.3mU和不完全弗氏佐剂(IFA)50μL、GAD3mU+IFA50μL、GAD0.03mU+IFA50μL、IFA50μL。8周龄时注射环磷酰胺200mg/kg加速糖尿病,定期检测血糖,眼内眦取血分离血清检测细胞因子白细胞介素(IL)4和干扰素(IFNγ)的变化,动态观察各组糖尿病发生发展的过程。28周时,全部处死,取脾、胸腺作淋巴细胞亚群测定,胰腺作病理组织学观察。结果GAD3mU+IFA50μL组小鼠无一只发生糖尿病,28周时血糖为(5.0+1.1)mmol/L;胰岛个数最多(8.2+2.3)个/张(P<0.01),胰岛炎评分最低(0.33+0.12)(P<0.01);血清中IL4的水平最高为(80+6)ng/L(P<0.01),IFNγ水平最低为(327±48)ng/L;CD8+/CD4+比值最大(P<0.01),在脾脏中为0.524±0.133,胸腺中为0.428±0.021。结论NOD小鼠在3周龄时腹腔注射CAD3mU+IFA50μL混合物比其他剂量组免疫调节效果好,较好地通过调节胸腺,脾淋巴细胞亚群分类,并通过淋巴细胞分泌Th1类因子和Th2类因子来调节Th0细胞的转化,从而抑制NOD小鼠胰岛炎,胰岛β细胞破坏减少,GAD3mU剂量组免疫干预NOD小鼠糖尿病的发生效果最好。     

Examination of the immunosuppressive effect of delta9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes

delta9-Tetrahydrocannabinol (delta9-THC) is capable of modulating a variety of immune responses, but has not been evaluated in models of immune-based diabetes. The objectives of the present study were: (a) to investigate the effect of delta9-THC in an established model of multiple low dose streptozotocin (MLDSTZ)-induced autoimmune diabetes; and (b) to determine the contribution of the immune response in the MLDSTZ model. CD-1 mice were treated with 40 mg/kg STZ for 5 days in the presence or absence of delta9-THC treatment. delta9-THC administered orally in corn oil at 150 mg/kg for 11 days attenuated, in a transient manner, the MLDSTZ-induced elevation in serum glucose and loss of pancreatic insulin. MLDSTZ-induced insulitis and increases in IFN-gamma, TNFalpha and IL-12 mRNA expression were all reduced on Day 11 by co-administration of delta9-THC. In separate studies, six doses of delta9-THC, given after completion of STZ treatment, was found equally effective in attenuating mice from MLDSTZ-induced diabetes. Studies performed using B6C3F1 mice showed moderate hyperglycemia and a significant reduction in pancreatic insulin by MLDSTZ in the absence of insulitis. In addition, MLDSTZ produced a less pronounced hyperglycemia compared to CD-1 mice that was not attenuated by delta9-THC. These results suggest that MLDSTZ can initiate direct beta-cell damage, thereby augmenting the destruction of beta-cells by the immune system. Moreover, these results indicate that delta9-THC is capable of attenuating the severity of the autoimmune response in this experimental model of autoimmune diabetes.     

Long-term inhibition of dipeptidyl-peptidase 4 reduces islet infiltration and downregulates IL-1β and IL-12 in NOD mice

Dipeptidyl-peptidase 4 (DPP-4) inhibitor (sitagliptin) is a novel anti-hyperglycemia drug in the treatment of type 2 diabetes. However, its potential in type 1 diabetes is still unclear. Recent studies show that increased infection, especially respiratory tract infection, is significantly associated with DPP-4 inhibitors. In this study, we aimed to explore the effects of long-term inhibition of DPP- 4 on innate immunity in type 1 diabetes. Forty mice were randomly divided into 4 groups (n = 10 in each group): control group, lipopolysaccharide (LPS) group, sitagliptin group and sitagliptin + LPS group. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α and IFN-γ were measured with Mesco Scale Discovery multiplexed-assay kit. Immunohistochemistry staining of pancreases was performed and insulitis scores for each islet were determined. The results showed that DPP-4 inhibition has no effect on incident rate of diabetes and metabolic parameters in NOD mice. Long-term inhibition of DPP-4 reduced CD4+T cells to infiltrate into islets and ameliorated insulitis in NOD mice. DPP-4 inhibition downregulated serum interleukin IL-1β and IL-12 in NOD mice. However, it had no significant effect on LPS-induced IL-1β, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in NOD mice. In conclusion, Long-term inhibition of DPP-4 exists anti-inflammatory effect in type 1 diabetes probably by reducing CD4+T cells to infiltrate into islets and downregulating L-1β and IL-12 in serum.     

人白细胞介素24真核表达载体的构建及其在HepG2细胞中的表达

目的 构建人白细胞介素24(human interleukin-24,hIL-24)真核表达载体,并在HepG2细胞中稳定表达,为进一步研究其抗肿瘤作用奠定基础.方法 采用逆转录聚合酶链反应(RT-PCR),从植物血凝素活化的人外周血单个核细胞中克隆得到hIL-24基因目的 片段.应用DNA重组技术将IL-24PCR产物双酶切后定向克隆至真核表达载体pcDNA3.1(+),转化大肠杆菌DHSα获得重组载体,进行PCR、酶切及测序鉴定.应用脂质体将鉴定正确的重组质粒转染至HepG2细胞,用G418筛选稳定转染细胞株.采用RT-PCR检测稳定转染细胞HepG2中IL-24 mRNA的表达.结果 通过RT-PCR获得与预期大小一致约600 bp的IL-24基因片段;重组载体pcDNA3.1(+)-IL-24经PCR、双酶切及测序证实,IL-24 eDNA片段已正确插入真核表达载体中;在稳定转染的HepG2细胞株中可见到IL-24 mRNA表达.结论 成功构建了hIL-24真核表达载体pcDNA3.1(+)-IL-24,并获得了稳定转染该重组质粒的HepG2细胞株.     

核心蛋白聚糖协同白细胞介素24对人外周血单个核细胞作用的体外研究

目的 探讨核心蛋白聚糖(decorin,DCN)联合白细胞介素24(interleukin-24,IL-24)对人外周血单个核细胞(human peripheral blood mononuclear cell,PBMC)增殖及分泌干扰素γ(Interferon-γ,IFN-γ)的影响.方法 构建重组质粒pcDNA3.1(+)-DCN和pcDNA3.1(+)-IL-24,并利用脂质体将两种质粒转染PBMC.根据转染质粒的不同将PBMC分为空白对照组、脂质体组、空质粒组、DCN组、IL-24组、DCN与IL-24联合组.采用四甲基偶氮唑蓝比色法检测PBMC的增殖,ELISA测定细胞培养上清中IFN-γ的表达,流式细胞技术检测PBMC表面程序性死亡分子1(PD-1)的表达.采用LSD-t检验进行统计学分析.结果 重组质粒pcDNA3.1(+)-IL-24构建成功.与其他组相比,DCN与IL-24联合能显著提高PBMC增殖率和IFN-γ分泌量,同时也能上调PD-1的表达水平.结论 DCN与IL-24双基因联合在体外能促进PBMC的增殖,并能增强PBMC的功能.     

1,25-二羟基维生素D_3对环磷酰胺处理的NOD小鼠糖尿病的影响

目的　探讨 1,2 5 -二羟基维生素 D3 对环磷酰胺促发的 NOD鼠 1型糖尿病的预防作用。方法　N OD鼠从离乳后隔日接受 1,2 5 -二羟基维生素 D3 治疗 ,第 10周龄给予环磷酰胺 30 0 m g/ kg,观察 1,2 5 -二羟基维生素 D3 对环磷酰胺处理的 NOD鼠糖尿病发病率和胰岛炎的影响 ,及对 Th1、Th2细胞因子 m RNA表达的影响。结果　 1,2 5 -二羟基维生素 D3 处理组糖尿病发病率为 17% ,明显低于对照组 6 7% (P<0 .0 5 ) ,且胰岛炎严重程度也明显减轻。处理组胰腺 TNT- α、IFN- γ m RNA的表达较对照组明显降低 ,而 IL- 10 m RNA的表达无明显改变。结论　 1,2 5 -二羟基维生素 D3 可以预防 NOD鼠环磷酰胺诱发的糖尿病的发生 ,其机制可能与纠正 Th1型细胞因子与 Th2型细胞因子比例失衡有关     

Increases in the expression levels of aquaporin-2 and aquaporin-3 in the renal collecting tubules alleviate dehydration associated with polyuria in diabetes mellitus

Enhanced expression of renal aquaporin-2 (AQP2) has been reported when polyuria occurs in diabetic animal models. The purpose of this study was to clarify the possibility that increased AQP2 expression in the kidneys play a role as a compensatory mechanism to alleviate diabetic dehydration. Lithium carbonate (Li?CO?), which decreases the renal expression of AQPs, was administered to streptozotocin (STZ)-induced model mice of type I diabetes mellitus (STZ mice), to investigate the relationship between urine volume and renal AQP expression. Plasma glucose and urine glucose levels were similar between STZ mice given feed containing Li?CO? for 10 d and un-treated STZ mice. Urine volume increased to 70 ml/d for the Li?CO?-treated STZ mice, compared to 36 ml/d for un-treated STZ mice. No changes were observed in creatinine clearance or the mRNA expression levels of sodium myo-inositol transporter and taurine transporter, which are genes associated with the regulation of osmotic pressure in the kidney, in the Li?CO?-treated STZ mice relative to un-treated STZ mice. Protein expression levels of AQP2 and aquaporin-3 (AQP3) of the renal inner medulla were significantly decreased in the Li?CO?-treated STZ mice, compared to levels in the STZ group. This study revealed that the decreased expression levels of AQP2 and AQP3 in the kidney increased the urine volume in mice without a change in urinary osmotic pressure. The results of this study suggest that the increased renal AQP2 and AQP3 expression, in the setting of polyuria, physiologically serves as a compensatory mechanism to alleviate dehydration in diabetes mellitus.