Objective:To explore the molecular mechanism of dynamin-related protein 1 (Drp1) -mediated mitochondrial energy metabolism involved in renal ischemia-reperfusion injury.Methods:The experiment was conducted on October 14, 2020. Male Wistar rats aged 8-10 weeks were randomly divided into a normal control group, a sham operation group, a model group, and a Drp1 inhibitor group, with 5 rats in each group and weight of 0.25-0.30 kg for each rat. The rat model of acute renal injury induced by renal ischemia-reperfusion was established. The rats in the Drp1 inhibitor group were intraperitoneally injected with mitochondrial division inhibitor 1 (Mdivi-1) of 20 mg/kg body weight, and the other groups were injected with normal saline of the same volume. Serum and kidney tissue were retained 24 hours after the model was made. The serum creatinine level, pathological change of renal tissue, apoptosis of renal tissue cells, mitochondrial ultrastructure, and mitochondrial ATPase activity were compared between the groups. The HK-2 cell hypoxia and reoxygenation models were established in vitro. The changes of mitochondrial membrane potential were detected by JC-1 staining after treatment. Analysis of variance was used.Results:Compared with those in the sham operation group, the serum creatinine in the model group was significantly increased [(41.12±1.895) μmol/L vs. (48.68±2.065) μmol/L], the renal tubule injury score was increased [(1.29±0.426) points vs. (6.50±0.577) points], the number of apoptosis in renal tissue was increased [(2.40±0.547) vs. (10.20±1.095)], the mitochondrial damage was more obvious under electron microscope, and the activity of mitochondrial ATPase was decreased [(6.38±0.321) U/mg prot vs. (4.18±0.198) U/mg prot]; in the HK-2 cell hypoxia and reoxygenation models, the proportion of cells with decreased mitochondrial membrane potential increased in the model group compared with that in the sham operation group [(9.81±0.251)% vs. (4.24±0.598)%], with statistically significant differences (all P<0.05). Compared with those in the model group, the serum creatinine in the Drp1 inhibitor group was decreased [(48.68±2.065) μmol/L vs. (43.28±0.895) μmol/L], the renal tubule injury score was decreased [(6.50±0.577) points vs. (4.50±0.578) points], the number of apoptosis of renal tissue cells was decreased [(10.20±1.095) vs. (6.60±1.140)], the mitochondrial structure damage was reduced, and the activity of mitochondrial ATPase was increased [(4.18±0.198) U/mg prot vs. (5.16±0.628) U/mg prot]; in the HK-2 cell hypoxia and reoxygenation models, the proportion of cells with decreased mitochondrial membrane potential decreased in the Drp1 inhibitor group compared with that in model group [(5.90±0.360)% vs. (9.81±0.251)%], with statistically significant differences (all P<0.05). Conclusion:Selective inhibition of Drp1 can effectively improve the energy metabolism disorder, reduce the cell apoptosis, and alleviate the renal ischemia-reperfusion injury by inhibiting the mitochondrial division.

目的 研究人神经丝中分子量亚单位多肽(NFM)的免疫原性及其抗体的特异性,为NFM单克隆抗体(McAb)的制备及ELISA检测方法的建立奠定基础.方法 分析人、大鼠、小鼠NFM氨基酸序列,选择人NFM4段肽P1、P2、P3、P4,人工合成并与匙孔槭血蓝蛋白(KLH)偶联,免疫小鼠收获血清,ELISA检测抗体效价,用Western blotting及免疫组化(IHC)检测各抗体与人、大鼠、小鼠及体外表达的NFM的反应性.结果 4种多肽具有较强的免疫原性,产生了高效价抗体,IHC结果显示,4种抗体均能与人脑组织胶质瘤、大鼠和小鼠脑组织中的NFM反应,Wesntern blotting结果显示,抗P1、P4抗体可与人脑组织胶质瘤、大鼠和小鼠脑组织中NFM反应,抗P1抗体出现2个条带;抗P1、P2、P3抗体均能与原核表达的NFM反应.结论 所选择4段多肽具有较好的免疫原性,小鼠所产生抗体能与人、大鼠和小鼠脑组织及体外表达的NFM反应,可进一步用于NFM McAb的制备.

Objective To optimize conditions for rat pancreatic islets isolation and purification,and provide experimental data for research on the pathogenesis of islet injury in diabetes and application of islet regeneration.Methods Influences of different pancreatic perfusion volumes and digestion time on rat pancreatic islets isolation through intraductal collagenase V perfusion in situ were observed.Effects on islets purification were compared between classical discontinuous Ficoll density gradient centrifugation and Histopaque 1077 density gradient centrifugation.Afterwards,the islets were examined and their morphology,quantity,purity and function were evaluated in vitro.Results Histopaque 1077 density gradient centrifugation could yield more islets of high quality(P<0.01).Insulin release by the islets through the two different methods under high glucose condition has no differentiation(P>0.05).Islets perfusion volumes and digestion time played significant roles in rat islets extraction.Conclusion Histopaque 1077 density gradient centrifugation,with simple operation and high yield,has a prospect to become the most effective method for rat islets purification and it will be more useful in clinical and basic research in the future.

目的:对比分析磺脲类、双胍类联合用药与盐酸吡格列酮、磺脲类、双胍类3联用药治疗2型糖尿病的降糖降脂疗效。方法:采用横断面调查方法,分别收集目前正在接受磺脲类、双胍类联合治疗和磺脲类、双胍类、盐酸吡格列酮3联治疗的共187例T2DM现患病例,分为两组。对两组患者的血糖、血脂、HbA1c、BMI值并进行比较。结果:Ⅱ组患者空腹血糖、餐后血糖、HbA1c显著低于Ⅰ组,且P值均<0.05。3联用药使糖化血红蛋白达标率明显增加,同时血脂检测中的高密度脂蛋白升高,据有统计学意义。结论:在磺脲类、双胍类联合用药方案中加用盐酸吡格列酮有利于进一步降低血糖、调节血脂,增强疗效。

Objective To investigate clinical characteristics and associated cardiovascular risk factors in prehypertensive patients with impaired glucose regulation(IGR).Methods 2 158 residents aged 35-75 years old were enrolled by the cross-sectional and cluster sampling methods from 4 cities in Shandong,of which 865 subjects were prehypertensive.All the subjects were divided into three groups: the simple prehypertention group(groupⅠ,n=510),the prehypertension with impaired glucose regulation group(groupⅡ,n=278) and the prehypertension with diabetes group(group Ⅲ,n=77).The clinical characteristics and associated cardiovascular risk factors were compared among the three groups.The risk factors of hyperglycemia were analyzed by binary logistic regression analysis.Results The prevalence of IGR was 32.1% in prehypertensive population.The values of age,BMI,waist circumference,CHOL,TG and LDL-C in group Ⅱwere higher compared with groupⅠ(P0.01).Age,WHR and TG in group Ⅲ showed a higher level compared with groups Ⅰ and Ⅱ(P0.05 or P0.01).The values of waist circumference,CHOL,LDL-C in group II were obviously higher compared with group Ⅰ(P0.01).The values of age,WHR and TG in group Ⅲ were obviously higher than those in group Ⅰ and Ⅱ(P0.05 or P0.01).The values of waist circumference,CHOL and LDL-C in group Ⅲ were higher than those in group Ⅰ(P0.01).The value of HDL-C in the group Ⅲwas lower compared with groups I and II(P0.05).The detection rates of obesity and hyperlipidemia were higher in groupⅡand groupⅢ(P0.05).Patients in groupⅡand group Ⅲ were more likely to have 2 or more cardiovascular risk factors than group Ⅰ(P0.05 or P0.01).Age(OR=1.04,95%CI: 1.02-1.05),BMI(OR=1.05,95%CI: 1.01-1.10) and LDL-C(OR=1.22,95%CI:1.02-1.46) proved to be the independent predictors for the impaired glucose regulation(all P0.05 or P0.01).Conclusion Prehypertension with impaired glucose regulation is frequently accompanied with obesity and hyperlipidemia.Prehypertensive patients with higher BMI,LDL-C,or older age were more likely to have impaired glucose regulation.

Objective To analyze the influence and forecast value of stress hyperglycemia on the recovery of daily living activity in stroke patient.Methods The clinical data of 459 non-diabetics stroke patients was retrospectively analyzed.The patients were devide into three groups according to the fasting plasma glucose level.They were the euglycemia group(FBG6.1 mmol/L),the mild stress hyperglycemia group(6.1 mmol/L≤FBG7.0 mmol/L) and the severe stress hyperglycemia group(FBG≥7.0 mmol/L).The statistical data included age,diseases history,blood biochemistry test,blood coagulability and hemostatic function test,CT,MRI and Activities of Daily Living Assessment(ADL).PASW 18.0 was used for the statistical analysis and statistical significance was set at P0.05.Results The risk of stress hyperglycemia was higher in senile patients(65 years old) with atrial fibrillation,hypertension or hypertriglyceridemia.Cerebral hemispheric infarction was connected with stress hyperglycemia.At the same time,fasting plasma glucose(FBG).Prothrombin Time %(PT%).fibrinogen(Fib).D-dimer(D-Di) and blood urea nitrogen(BUN) were closely related to the ADL score.The ADL score of the mild stress hyperglycemia group and the severe stress hyperglycemia group was lower than that of the euglycemia group,while it was also lower in the severe stress hyperglycemia group than in the mild stress hyperglycemia group.Stress hyperglycemia was positively correlated with the high risk of activity disorder in stroke patients(rs=-0.264 3,P0.000 1).Conclusions Stress hyperglycemia in patients with cerebral infarction increases the risk of daily living activity disorder.

<正>调节性T细胞(regulatory T cells,Tregs)为一类特殊的T淋巴细胞亚群,因能够有效抑制自体免疫活性、预防人类的自体免疫性疾病而受到广泛关注。Tregs通过对其他免疫细胞的负调节发挥维持免疫稳态的作用。已知Tregs主要分为两类,天然的Tregs(nTregs)以及外周抗原诱导的Tregs(iTregs)。nTreg是源自

Objective To observe and evaluate the clinical effect of structured management mode of premixed insulin therapy in patients with type 2 diabetes.Methods In this study,48 patients with type 2 diabetes were randomly assigned to two groups.They received premixed insulin subcutaneously twice a day and then were followed up for 16 weeks.Patients in the structured management intervention group received 9 times supervision and intensive education and management by specialized education nurse.While patients in the control group only received 6 times generally supervision and education.All patients were required to receive laboratory examination before and after the treatment,including HbA1c,fasting C-peptide,7-time points blood sugar spectrum,et al and fill in related questionnaire.Adverse reactions were also observed.Results The levels of HbA1c and 7-time points blood sugar spectrum decreased in both groups,while were much lower in the structured management intervention group(P0.01 or P0.05).Behavior and cognitive significantly improved in the structured management intervention group compared to the control group.There were no significant differences of BMI and fasting C-peptide before and after treatment,also between two groups.Lower incidence of hypoglycemia was reported in the structured management intervention group(P0.05).Conclusion After the structured management intervention treatment,type 2 diabetes mellitus patients using the premixed insulin therapy have a better blood sugar control,a better behavior and cognitive change,and a lower risk of hypoglycemia.

MicroRNAs(miRNAs) are non-coding single strand RNA of short sequence,which could regulate gene expression at the post-transcriptional level. It widely exists in eukaryotic cells and plays an important role in their life process. miRNAs are closely related to insulin secretion as well as glucose regulation.There is close link between miRNAs and the development of diabetes as well. miRNAs also involve in the development of diabetic complications and may have the potential therapeutic value for diabetes and its complications. Reviewing the latest study of correlation between miRNAs, diabetes and its complications will be beneficial for exploring the potential therapeutic value of miRNAs on the treatment of diabetes.

目的探讨二十二碳六烯酸(DHA)对脂多糖(LPS)诱导小鼠急性肺损伤的预防保护作用。方法雄性昆明种小鼠随机分成对照组、DHA组和模型组。适应性喂养1周后,DHA组动物每天经灌胃给予500mg/kgDHA,对照组和模型组给予等体积的玉米油,连续2周。第15天,模型组和DHA组动物经腹腔注射给予LPS10mg/kg诱导内毒素性急性肺损伤;给予LPS后,记录各组动物死亡情况,进行死亡率比较。20h后乌拉坦麻醉各组小鼠,取肺脏进行病理学检查;称量肺组织,计算肺脏/体重比值;BCA法测定支气管肺泡灌洗液(BALF)中蛋白质含量。结果给予LPS后的20h内,DHA组小鼠死亡率为10%,模型组死亡率为33.3%,两者比较差异有统计学意义(P<0.05);模型组肺脏/体重比值明显升高,肺组织病理学观察可见肺泡间隔明显增厚,大量中性粒细胞浸润,BALF中总蛋白含量明显升高;与模型组相比,预给予DHA2周,可明显降低肺脏/体重比值,降低BALF中总蛋白含量,改善肺组织病理变化。结论DHA能够减轻小鼠内毒素性急性肺损伤。

内质网是一个动态的膜性细胞器,具有多种功能,包括蛋白质的合成、修饰、折叠、类固醇、脂质和糖原的合成以及钙的储存与钙稳态的维持等[1].内质网含有大量的伴侣蛋白、糖基化酶以及氧化还原酶,为新生肽链的折叠提供了优化的环境,同时内质网质量控制系统能通过内质网相关性降解(endo-plasmic reticulum associated degradation,ERAD)过程,降解非正确折叠或修饰的中间产物.

目的:探讨内质网应激(ERS)在2型糖尿病(T2DM)小鼠脂肪肝发生中的作用机制.方法:应用实时定量RT-PCR技术检测T2DM与非糖尿病小鼠肝脏ERS和脂代谢相关基因表达差异, 并进行血生化指标及肝脏形态学检测.结果:与同龄非T2DM小鼠相比T2DM小鼠表现为:(1)胰岛素抵抗、空腹血糖升高(30.76±4.52 vs 12.80±2.13, 14.73±2.74v s 4.61±1.12). (2)肝脏TG和F FA水平明显升高( P<0.01); 脂肪肝病变明显. (3)肝脏GRP78、XBP1、CHOP、EDEM1、GSK3β、apoB100、SREBP1c、ACCα及FAS的mRNA水平均显著上调( P<0.05). (4)血清TG、TC、LDL-C、FFA、ALT及AST显著升高( P<0.01).血清apoB100水平先升高, 后下降( P<0.05).结论:ERS参与调节肝脏脂质及apoB100的合成与代谢过程, 在T2DM小鼠脂肪肝发生过程中起着重要作用.

检测45例女性原发性甲状腺机能减退症(甲减)患者(观察组)与40例健康女性(对照组)的空腹血清游离甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、尿素氮(BUN)、肌酐(Cr)、尿酸(UA)、肌酐清除率(CCr),并进行相关性分析.结果 研究组BUN、Cr、UA均明显高于对照组,CCr显著低于对照组(P均<0.05);FT3与CCr呈正相关(r=0.665,P<0.05).但TSH、FT4与各肾功能指标均无明显相关(P＞0.05).认为女性原发性甲减患者常伴BUN、Cr、UA升高,CCr下降;其CCr水平下降与FT3关系密切.

Objective ApoE-/-/LDLR-/-/Leprdb/db,a triple-gene mutant(ALO) mouse has established for the first time,and has been used for study for the effects of allicin on hyperlipidemia as well as atherogenesis.Methods Six groups of mice were used(G1-G6).G1 and G2 were fed a chow diet and G3 and G4 were fed a high fat and high cholesterol diet(10% animal fat and 1.25% cholesterol),and G5 and G6 were fed a high fat,high chrosterol diet combined 20% sucrose drinking water.G2,G4 and G6 were treated with allicin.All mice were sacrificed at 3,5,7,11 and 15 weeks of age and then blood,liver as well as aorta were isolated for biochemical and morphological analysis(n=6).Results The level of TC,TG and LDL-C are decreased in the mice which received allicin compared to those mice received distilled water,although the level of HDL-C are not changed significantly in the groups(TC level,G2/G1,42.40±2.57 vs.45.40±6.72;G4/G3,106.90±5.37 vs.109.20±2.35 and G6/G5,115.45±1.27 vs.121.76±5.12).When feed with chow diet,hepatocytes are obviously changed compared to those mice received distilled water.Fed with 20% sucrose and high fat/cholesterol diet,effect of allicin is shown more affective,and the lipid drops in liver cell is became small and less than those mice given by distilled water as placebo.The morphology change of atherosclerosis in allicin groups shown slightly inhibited compared with that of placebo group.Conclusions These results indicated that triple gene mutation is contributed to severe hyperlipidemia and allicin has a role which inhibited the progress in development of dyslipidemia and atherogenesis in our unique ALO mice model.