Detection and Clinical Significance of Th17/Treg Cell-Related Factors in Patients with Gestational Diabetes Mellitus

Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.

The impact of Hypoglycemic Ziyabiti Tablets (HZT) on diabetes mellitus rats and its activity in cultured rat liver cells

Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan(ALX)at next two subsequent days to induce diabetes mellitus(DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose(FBG),total cholesterol(TC),total triglycerides(TG),high-density lipoprotein(HDL-C),fasting insulin(FI),insulin secretion(IS)and insulin sensitivity index(ISI)were measured.The IC_(50) of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury(Par),on lactate dehydrogenase(LDH)activity and on glucose consumption.Results HZT decreased FBG and TC(P <0.05),increased IS(P <0.05)and at 440 mg·kg^(-1)·d^(-1) increased FI(P < 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver.

Changes of activity of liver glycogen synthase in experimental diabetes mellitus rats

OBJECTIVE: To study the activity of liver glycogen synthase in analogous model of NIDDM rats. METHODS: Male Wistar rats were injected with low dose of streptozotocin (STZ) (30 mg/kg body weight) via tail vena and those animals with glucose tolerance impaired and level of insulin equal to or higher than that of the controls at 18th week were taken as the analogous rat model of NIDDM. The activity of liver glycogen synthase (GS) was assayed at the end of experiment. RESULTS: Type I-enzyme: 0.18 +/- 0.06 mumol/min.g versus 0.24 +/- 0.09 mumol/min.g, P

High-fat-diet induced obesity and diabetes mellitus in Th1 and Th2 biased mice strains:A brief overview and hypothesis

Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide.Mice are commonly used to study the pathogenesis of these two conditions.Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used.Several factors may influence the outcome of the studies done to study diet-induced obesity in mice.The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease.In this article,the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated.Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity.A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1-and Th2-biased mice strains were briefly analyzed.Based on the observations,it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1-and Th2-biased mice strains.For instance,in Th1-biased mice,adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver,it was found to be less.It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.

Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

AIM:In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8),the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated.In rats that were also diabetic(induced by streptozotocin,STZ),pancreatic regeneration was not observed.The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats. METHODS:Male Wistar rats were used for the experiments. Diabetes mellitus was induced by administering 60mg/kg body mass of STZ intraperitoneally(i.p.),then,on d 8, pancreatitis was induced by 200mg/100 g body mass Arg i.p.twice at an interval of 1 h.The animals were injected subcutaneously twice daily(at 7 a.m.and 7 p.m.)with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin(300g/L short- action and 700g/L intermediate-action insulin) for 14 d after pancreatitis induction.Following this the animals were killed and the serum amylase,glucose and insulin levels as well as the plasma glucagon levels,the pancreatic mass/body mass ratio(pm/bm),the pancreatic contents of DNA,protein,amylase,lipase and trypsinogen were measured.Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections. RESULTS:In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein,amylase and lipase vs the rats receiving only CCK-8 treatment.CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities,whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats. CONCLUSION:Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats, the simultaneous administration of exogenous insulin restored this effect.Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.

Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats

Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.

基于网络药理学和试验验证探讨茵陈蒿汤治疗糖尿病的作用机制

【目的】通过网络药理学、分子对接和试验验证的方法探讨茵陈蒿汤(YCHD)治疗糖尿病(DM)的作用机制。【方法】利用TCMSP、ETCM、UniProt、SwissTargetPrediction数据库及文献查阅等查找YCHD的活性成分和相关作用靶点;利用OMIM、PharmGkb、TTD、DrugBank数据库获取DM的疾病靶点。构建YCHD和DM的蛋白互作(PPI)网络图,对关键作用靶点进行GO功能和KEGG通路富集分析。采用AutoDockTool 1.5.7软件进行分子对接,预测活性成分和核心靶点的结合能。将细胞分为对照组(Control)、模型组(Model)及YCHD含药血清低(YCHD-L)、中(YCHD-M)、高(YCHD-H)剂量组,通过体外细胞试验检测诱导型一氧化氮合酶(iNOS)、环氧化酶2(COX2)、Toll样受体4(TLR4)、核因子κB(NF-κB)p65、白细胞介素-1β(IL1β)、IL6的mRNA表达水平,以及iNOS、COX2、髓样分化因子88(MyD88)、NF-κB p65蛋白表达水平,并对关键通路进行验证。【结果】共获得YCHD活性成分147个,DM疾病靶点486个,YCHD作用于DM的相关靶点基因57个,其中胰岛素(INS)、IL1β、肿瘤坏死因子(TNF)、B细胞中κ轻型多肽基因增强子的核因子1(NFKB1)、信号传导子和转录活化子1(STAT1)、白蛋白(ALB)、TLR4、IL1A、IL10、IL8等为关键靶基因。根据Counts值筛选出GO前十的条目中包含生物过程1条、细胞组分7条、分子功能2条,主要包括RNA聚合酶Ⅱ启动子转录的正调控、内质网膜、质膜、胞外区、核质、胞质溶胶、细胞质、膜的组成部分、相同蛋白质结合和蛋白质结合。KEGG通路富集分析显示,与NOD样受体、NF-κB、Toll样受体等炎症信号通路密切相关。分子对接结果显示,YCHD的活性有效成分与主要靶点具有良好的结合能力。体外试验结果表明,与对照组相比,模型组细胞TLR4、iNOS、COX2、NF-κB p65、IL1β和IL6 mRNA表达水平及iNOS、COX2、MyD88、NF-κB p65蛋白表达水平均显著升高(P<0.05);与模型组相比,YCHD-L、YCHD-M、YCHD-H组细胞iNOS、COX2、IL1β和IL6 mRNA表达水平及iNOS、COX2蛋白表达水平均显著降低(P<0.05),YCHD-M、YCHD-H组细胞TLR4、NF-κB p65 mRNA水平显著降低(P<0.05),YCHD-H组细胞MyD88、NF-κB p65蛋白表达水平显著降低(P<0.05)。【结论】YCHD可能通过多成分、多靶点,调控TLR4、NF-κB等多条炎症信号通路,发挥抗DM的作用。以YCHD-H组对炎症信号通路相关指标的抑制最明显。

Effects of Electroacupuncture at Weiwanxiashu and Zusanli Points on Blood Glucose and Plasma Pancreatic Glucagon Contents in Diabetic Rabbits

The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by Alloxan. It is found that acupuncture at Weiwanxiashu point can significantly lower the BG content and inhibit release of PG; no significant changes in BG and PG are found when acupuncture is given at Zusanli (ST 36) point alone, however BG and PG contents decrease more obviously when acupuncture employed at both Zusanli and Weiwanxiashu, suggesting that Zusanli has a marked synergetic action with Weiwanxiashu.

1型糖尿病患者Th细胞亚群和细胞因子的变化及其意义

目的 通过观察新诊断的 1型糖尿病患者中Th细胞亚群及其细胞因子的变化 ,了解 1型糖尿病患者中Th细胞亚群免疫功能的改变。方法 正常对照组 (N组 )和糖尿病组 (D组 )各 2 0例 ,糖尿病组再分为治疗前和治疗后 ,N组和D组 (治疗前后 )均测定空腹血糖 (FBG)、餐后 2h血糖 (P2hG)、糖化血红蛋白(HbAlc)、T淋巴细胞亚群、NK细胞活性、SIL 2R和细胞因子IFN γ、IL 4。结果 ①治疗前D组CD4/CD8比值明显低于N组和治疗后 (P值均 <0 0 1) ;NK细胞活性也明显低于N组和治疗后 (P值均 <0 0 1) ;而治疗前D组SIL 2R水平明显高于N组和治疗后 (P值均 <0 0 1)。治疗 12个月后 ,D组的CD4/CD8比值、NK细胞活性和SIL 2R水平均有不同程度的恢复 ,但与N组相比差异仍有统计学意义 (P <0 0 5 )。②治疗前D组的IFN γ值明显高于N组 ,P <0 0 1,治疗后D组IFN γ值与N组的差异则无统计学差异 ;而IL 4值则无论在治疗前和治疗 12个月后均明显低于N组 ,P <0 0 1。结论 在新诊断的 1型糖尿病患者中存在着T淋巴细胞亚群、Th淋巴细胞亚群及其分泌的细胞因子的改变 ,提示 1型糖尿病的发生和发展与免疫功能的改变是密切相关的。

基于团体游戏疗法的健康教育对老年糖尿病病人的影响

目的:探讨基于团体游戏疗法的健康教育对老年糖尿病病人血糖水平、自我管理知识、态度、行为的影响,为团体游戏疗法在糖尿病健康教育领域的应用提供参考。方法:便利选取2022年7月—11月昆明市某社区卫生服务中心辖区内的老年糖尿病病人60例作为研究对象,随机分为对照组和干预组,各30例。对照组实施社区常规糖尿病健康教育,干预组在对照组的基础上实施基于团体游戏疗法的健康教育,干预3个月。比较两组干预前后的病人的血糖控制情况与病人的自我管理知识、态度和行为的评分,和干预组病人对本研究的满意度评价。结果:干预后,干预组糖化血红蛋白(HbA1c)测量值低于干预前,差异有统计学意义(P<0.05);干预组糖尿病自我管理知识、态度、行为评分明显高于对照组,差异有统计学意义(P<0.05);干预组病人的干预满意度得分为46.00(43.75,48.00),93.30%的病人对本研究干预模式感到非常满意。结论:基于团体游戏疗法的健康教育干预模式在提高老年糖尿病病人的自我管理知识、态度和行为方面的效果优于社区常规健康教育,在降低老年糖尿病病人HbA1c方面也有一定效果;此外,该干预方案实施获得了较高的满意度,为老年糖尿病病人的健康教育提供了新的干预思路。

妊娠初期Th细胞因子与妊娠期糖尿病发生的相关性及对产后糖代谢异常的预测效能研究

目的分析妊娠初期辅助型T细胞(Th细胞)因子与妊娠期糖尿病发生的相关性及对产后糖代谢异常的预测效能。方法选取2019年1月至2021年1月在浙江省诸暨市妇幼保健院建档行规律产检、分娩的238例孕妇作为研究对象。在妊娠初期检测血清Th1细胞因子及Th2细胞因子,根据妊娠24~28周行75g葡萄糖耐量试验(OGTT)结果分为妊娠期糖尿病组(n=42)和对照组(n=196),比较两组妊娠初期Th细胞因子水平及其比值,通过受试者工作特征(ROC)曲线下面积(AUC)评价妊娠初期Th细胞因子对产后糖代谢异常的预测效能。结果妊娠期糖尿病组妊娠初期血清肿瘤坏死因子-α(TNF-α)水平高于对照组,白介素-10(IL-10)水平低于对照组,TNF-α/IL-4、IL-2/IL-10、γ-IFN/IL-10、TNF-α/IL-10均大于对照组,差异具有统计学意义(P<0.05);妊娠期糖尿病组妊娠24~28周胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)水平均高于对照组,差异具有统计学意义(P<0.05);经多因素Logistic回归分析,TNF-α、IL-10和TNF-α/IL-10均是妊娠期糖尿病发生的独立预测因素(P<0.05);经Pearson相关性分析,妊娠期糖尿病患者妊娠初期TNF-α/IL-10与妊娠24~28周HOMA-IR、HOMA-β均呈正相关(P<0.05);经ROC曲线分析,妊娠初期TNF-α/IL-10预测妊娠期糖尿病患者产后糖代谢异常的AUC为0.912。结论妊娠初期TNF-α/IL-10增大与妊娠期糖尿病发生的关系密切,对产后糖代谢异常具有较好的预测效能,可能成为早期筛查妊娠期糖尿病的重要指标。

益生菌辅助应用对妊娠期糖尿病患者血糖控制和Th细胞因子的影响

目的探讨益生菌辅助应用对妊娠期糖尿病(GDM)患者血糖控制和Th细胞因子的影响。方法选取2021年4月—2022年4月温州医科大学附属第二医院收治的80例GDM患者,按照随机数字表法分为对照组(40例,常规治疗)和观察组(40例,益生菌联合常规治疗)。对比两组患者治疗效果,血糖、血脂控制情况,Th细胞因子水平,母婴结局。结果观察组总有效率为97.50%,高于对照组的85.00%(χ^(2)=3.914,P<0.05)。治疗后,观察组患者空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)及稳态模型胰岛素抵抗指数(HOMA-IR)均低于对照组[观察组:(5.28±0.57)mmol/L、(6.49±0.71)mmol/L、(6.30±0.69)%、(17.26±1.96)mU/L、(4.05±0.54);对照组:(5.76±0.62)mmol/L、(7.29±0.83)mmol/L、(6.98±0.74)%、(18.98±2.22)mU/L、(4.86±0.56)],胰岛β细胞分泌指数(HOMA-β)高于对照组[观察组:(193.93±20.69);对照组:(167.96±17.74)],差异均有统计学意义(均P<0.05)。治疗后,观察组患者总胆固醇(TC)、三酰甘油(TG)及低密度脂蛋白(LDL)均低于对照组,高密度脂蛋白(HDL)均高于对照组(均P<0.05)。治疗后,观察组患者白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)及肿瘤坏死因子-α(TNF-α)均低于对照组,白细胞介素-4(IL-4)、白细胞介素-10(IL-10)均高于对照组(均P<0.05)。观察组孕妇早产、剖宫产、羊水过多、产后感染、妊娠期高血压疾病、产后出血、低体质量儿、巨大儿、高胆红素血症及新生儿低血糖发生率均低于对照组(均P<0.05)。结论益生菌辅助治疗GDM患者可取得较好效果,可较好地控制血糖、血脂水平,改善Th细胞因子水平,改善母婴结局。

基于代谢组学探讨玄参-苍术联合二甲双胍治疗2型糖尿病大鼠作用机制

目的:采用代谢组学方法分析玄参-苍术联合二甲双胍治疗2型糖尿病大鼠的作用机制。方法:采用高脂饮食联合链脲佐菌素(streptozocin,STZ)建立2型糖尿病大鼠模型,分为空白组、模型组、阳性组和治疗组。治疗后6周,检测各组大鼠体质量、血糖、丙氨酸氨基转移酶、空腹血清胰岛素、核转录因子(NF-κB)、大鼠隐热蛋白(NLRP3)等指标水平,初步评价玄参-苍术联合二甲双胍对2型糖尿病大鼠的治疗作用。进一步采用UPLC-MS/MC非靶向代谢组学揭示各组之间的代谢谱,筛选差异代谢物并进行鉴别。结果:与阳性组比较,治疗组改善临床症状及降低餐后高血糖的作用更为明显(P﹤0.05),且可显著降低NF-κB和NLRP3水平(P﹤0.01)。通过代谢组学筛选出36种差异代谢物作为玄参-苍术联合二甲双胍治疗糖尿病作用机制的相关血清潜在生物标志物。D-谷氨酰胺和D-谷氨酸是玄参-苍术联合二甲双胍治疗糖尿病涉及的相关的代谢通路。结论:玄参-苍术联合二甲双胍治疗糖尿病有效,推测其机制是通过调节D-谷氨酰胺和D-谷氨酸代谢通路基因的表达以维持“谷氨酰胺-谷氨酸”动态平衡,抑制NF-κB/NLRP3通路激活,进而提高机体对胰岛素敏感性、调节糖脂代谢紊乱、减轻炎症反应。

葛根芩连汤治疗2型糖尿病研究进展

葛根芩连汤治疗2型糖尿病(diabetes mellitus type 2,T2DM),可降低血糖水平、改善糖脂代谢及胰岛功能等。实验研究也表明,葛根芩连汤可通过改善胰岛素抵抗、调节糖脂代谢、调节肠道菌群、抑制炎症因子表达等控制血糖水平,缓解T2DM病情。目前的研究仍存在不足之处:葛根芩连汤在治疗T2DM的应用中,缺乏统一规范的疗效判定标准及大量的临床样本,其具体的分子生物学机制尚不明确。此外,葛根芩连汤原方中“两”的剂量历来没有统一的规范,以往的临床应用与研究中,各医家对其具体剂量的使用均有不同,主要从临床经验入手来确定其具体用量,缺乏严谨性,不便于临床规范应用。今后,应结合现代分子生物学技术探讨葛根芩连汤治疗T2DM的具体机制,并建立统一规范的疗效判定标准和剂量使用标准,充分发挥中医药治疗T2DM的优势,为提高疗效及扩大临床应用补充有利依据。

2型糖尿病动物模型在牙科种植领域中的应用

2型糖尿病是以长期高血糖为特征的代谢性疾病,可以诱发多种口腔疾病,如根面龋、牙周病等,且对种植骨代谢有负面影响,主要是体现在高血糖所致的炎症状态、血管生成减少、内皮功能障碍、内皮依赖性血管舒张功能受损、破骨活动增强和骨修复减弱的骨代谢平衡失调等方面。其在骨骼与血管系统的并发症常导致拔牙创骨愈合减缓,引导骨再生术后新骨生成率低,种植体骨结合失败率高和种植体周围骨丧失加剧。建立2型糖尿病动物模型在种植体表面改性、高血糖情况下种植适应症的探索、种植体周围炎病理生理学的研究,以及治疗方法创新或药物评估等方面发挥了关键作用。本综述将目前实验动物常用的2型糖尿病造模方法和成模指标进行分类总结,主要讨论了不同实验动物2型糖尿病模型在牙科种植领域的应用,以期为牙科种植研究中2型糖尿病动物模型的选取提供新的思路。

综合生物信息学、网络药理学、分子对接及实验验证探讨补肾健脾方改善2型糖尿病的作用机制

【目的】综合生物信息学、网络药理学和分子对接探讨补肾健脾方(由淫羊藿、鹿角胶、黄芪、山药等组成)改善2型糖尿病(T2DM)的作用机制,并通过动物实验验证。【方法】通过Mfuzz分析正常样本由糖耐量异常转变为T2DM的模块基因,并通过差异分析进一步筛选T2DM的疾病靶点;通过TCMSP、BATMAN数据库筛选补肾健脾方的活性成分及其作用靶点,随后获取补肾健脾方治疗T2DM的靶点并分析生物功能。比较补肾健脾方治疗组db/db小鼠胰岛功能、氧化应激指标、胰腺细胞凋亡与对照组的差异。【结果】共筛选出77个补肾健脾方的作用靶点,通过富集分析,77个靶点与氧化应激过程关系密切,并进一步筛选出2个核心靶点FOS、NOTCH1,通过分子对接证明了补肾健脾方主要活性成分与核心靶点结合稳定。最后,通过动物实验证明,与对照组比较,治疗组db/db小鼠稳态模型评估的胰岛素抵抗指数(HOMA-IR)升高,氧化应激指标丙二醛(MDA)降低、超氧化物歧化酶(SOD)活性升高,胰腺组织FOS、NOTCH1表达量降低,胰腺组织凋亡蛋白Bax和Caspase-3表达量降低、凋亡抑制蛋白Bcl-2表达量升高(P<0.05或P<0.01)。【结论】补肾健脾方可通过减轻氧化应激,降低胰岛细胞凋亡,从而改善胰岛素抵抗以延缓T2DM的进展。

抗衰老片治疗2型糖尿病能量代谢的网络药理学分析及实验验证

目的基于网络药理学和体内实验探究抗衰老片治疗2型糖尿病(type 2 diabetes mellitus,T2DM)能量代谢的作用机制。方法通过TCMSP筛选抗衰老片中药材的主要化学成分及其靶点,并通过文献调研、Pubchem对抗衰老片中药材的主要成分进行补充,经SwissTargetPrediction数据库预测靶点;通过GeneCards、OMIM数据库获取2型糖尿病、能量代谢相关靶点;通过Venny 2.1.0平台获得抗衰老片与2型糖尿病、能量代谢的共同靶点;基于STRING数据库和Cytoscape 3.8.0软件构建药物与疾病共同靶点的蛋白互作网络图;基于R语言进行GO和KEGG富集分析;通过ELISA、Western Blot法验证抗衰老片对2型糖尿病大鼠能量代谢的作用。结果筛选出抗衰老片223个活性成分和1232个靶点,2型糖尿病靶点10871个,能量代谢相关靶点9013个;抗衰老片、2型糖尿病和能量代谢的共同靶点625个。关键靶点在KEGG富集分析主要涉及MAPK、PI3K/Akt、JAK/STAT等信号通路。实验结果表明,与模型组相比,抗衰老片能显著降低2型糖尿病大鼠血糖水平,改善能量代谢相关指标含量,显著上调PI3K/Akt蛋白的磷酸化水平(P<0.05)。结论抗衰老片可调节2型糖尿病能量代谢,其作用机制可能与PI3K/Akt信号通路相关。

不同剂量STZ诱导小鼠糖尿病模型的发病机制

目的:探讨不同剂量链脲佐菌素(STZ)多次注射诱导小鼠糖尿病模型的发生机制以及糖尿病的发生与自身免疫应答的关系。方法:昆明小鼠40只随机分为正常对照组(Ⅰ组)及20、40、80 mg.kg-1STZ组(Ⅱ、Ⅲ、Ⅳ组)。腹腔注射不同剂量STZ诱导小鼠糖尿病作为动物模型。葡萄糖(Glu)测定试剂盒与尿液分析试纸条联合检测小鼠血糖和尿糖的变化,光镜观察胰岛的组织学改变情况,ELISA间接法检测小鼠血清中胰岛素抗体(IAA)的水平,淋巴细胞转化试验(MTT法)检测小鼠胸腺和脾脏的T淋巴细胞功能。结果:对照组血糖基本无变化,模型组血糖值随时间增加而增加;注射STZ后第4周,尿糖结果Ⅰ组均为(-);Ⅱ组中5只(-),其余均>+;Ⅲ组中2只(-),其余均>;Ⅳ组均>。不同剂量STZ诱导小鼠胰岛β细胞损伤的病理改变和程度均有所差异。Ⅱ组和Ⅲ组的IAA高于对照组(P<0.05),而Ⅳ组与对照组比较差异无显著性(P>0.05)。与对照组比较,Ⅱ组和Ⅲ组的脾细胞(成熟的T淋巴细胞)对ConA的刺激表现为功能增强,而胸腺细胞(不成熟的T淋巴细胞)对ConA的刺激则表现为功能降低;但Ⅳ组与对照组比较差异无显著性(P>0.05)。结论:3种剂量STZ均可诱导不同程度的糖尿病发生。大剂量STZ(80 mg.kg-1)可诱导小鼠产生2型糖尿病;而小剂量STZ(20和40 mg.kg-1)则诱导产生1型糖尿病,以40 mg.kg-1STZ诱导的1型糖尿病的效果为最佳。

2型糖尿病大鼠模型的建立及其糖代谢特征分析

目的 建立一种接近于人类普通型 2型糖尿病大鼠模型。方法 8周龄SD大鼠高热量饮食喂养 2个月后给予小剂量STZ建立 2型糖尿病模型 ,然后进行胰岛素 葡萄糖耐量试验、胰岛免疫组化及其图像分析 ,并与大、小剂量STZ、单纯高热量饮食等各组大鼠相应指标比较。结果 高热量饮食一段时间后给予小剂量STZ的大鼠模型外周胰岛素敏感性降低 ,胰岛素合成和分泌相对于单纯高热量饮食组大鼠降低 ,但仍高于正常对照组。结论 该模型大鼠具有外周胰岛素抵抗和胰岛功能仅轻微受损等特征 ,具有类似人类 2型糖尿病的临床表现 。