目的 探讨老年膝骨关节炎病人血清UA水平与软骨组织中UA转运蛋白的相关性. 方法 收集2018～2019年就诊于河北省人民医院骨科的老年膝骨关节炎(KOA)病人30例.以所有入选者UA中位数水平(254.6μmol/L)将病人分为血清UA<254.6μmol/L组(A组)和UA≥254.6μmol/L组(B组),检测并比较2组软骨组织中葡萄糖易化转运蛋白9(GLUT9)和尿酸盐转运蛋白1(URAT1)的mRNA和蛋白的表达水平. 结果 与B组相比,A组病人的体质量、BMI较小,VAS评分较低,差异均有统计学意义(P<0.05).Pearson相关分析显示,VAS评分与UA水平呈正相关(r=0.396,P<0.05).B组病人关节软骨中GLUT9、URAT1的mRNA和蛋白表达水平均较A组明显升高,差异有统计学意义(P<0.05). 结论 UA水平的升高可能通过增加软骨中GLUT9及URAT1蛋白的表达,使软骨细胞内UA水平升高,诱导软骨细胞氧化损伤,从而参与KOA的发病.

目的 探讨miR-21靶向调控配体蛋白1(Jagged-1)在心肌梗死大鼠心肌纤维化的作用.方法 将大鼠随机分成4组,每组15只:假手术组、模型组、阴性对照组和实验组.假手术组、模型组大鼠心脏冠状动脉注射磷酸盐缓冲液(phosphate buffer solution,PBS),阴性对照组和实验组大鼠分别心脏冠状动脉注射rAAV9-miR-21-inhibitors-NC病毒载体和rAAV9-miR-21-inhibitors病毒载体.采用结扎左前降支冠状动脉的方法来构建心肌梗死大鼠模型.氯化三苯基四氮唑(triphenyl tetrazolium chloride,TTC)染色检测各组大鼠心肌梗死比例,免疫组化法检测心肌组织测Ⅰ、Ⅲ型胶原蛋白表达,Western blot检测各组大鼠心肌组织中α-平滑肌肌动蛋白(α-SMA)、跨膜融合蛋白1(Notch1)和配体蛋白1(Jagged-1)蛋白的表达.结果 假手术组、模型组、阴性对照组、实验组的心肌梗死比例分别为0,(57.48±6.58)％,(56.88±7.08)％ 和(21.06±3.33)％;Ⅰ型胶原蛋白的表达分别为1.01±0.05,4.75±0.32,4.55±0.52和1.89±0.08;Ⅲ型胶原蛋白的表达分别为0.99±0.08,7.82±0.18,7.85±0.14和2.15±0.26;α-SMA的相对表达量分别为1.00±0.04,5.78±0.22,5.75±0.25和2.56±0.38;Notch1的相对表达量分别为0.98±0.07,4.22±0.35,4.15±0.41和2.07±0.33;Jagged-1的相对表达量分别为1.01±0.06,4.38±0.25,4.33±0.31和1.78±0.17.模型组与假手术组比较,实验组与模型组比较,差异均有统计学意义(均P<0.05).结论 miR-21可靶向调控Jagged-1的表达,抑制心肌梗死大鼠的心肌纤维化.

目的:探讨妊娠糖尿病伴亚临床甲减对孕妇骨密度及骨钙素、25-羟基维生素D的影响.方法:以本院内分泌科确诊的妊娠期糖尿病伴亚临床甲减孕妇120例为观察组,同期产前检查健康孕妇120例为对照组,检测两组孕妇骨密度(BMD)及骨钙素(OC)、25-羟基维生素D3 (25-OH-VD3),并观察母婴妊娠结局.结果:观察组骨量正常率(72.5％)低于对照组(85.0％),骨量减少发生率(20.0％)和OC(9.86±0.13μg/L)高于对照组(5.0％、7.21±0.15μg/L),25-OH-VD(16.09±5.34μg/L)和跟骨BMD水平(0.91±0.18 g/cm2)低于对照组(18.96±6.36μg/L、1.14±0.21g/cm2)(均P＜0.05);观察组新生儿低出生体质量(20.0％)和新生儿窒息发生率(10.0％)高于对照组(5.0％、1.7％).结论:妊娠糖尿病伴亚临床甲减可降低孕妇的骨密度,影响骨钙素、25-羟基维生素D表达水平,增加新生儿窒息、低体重风险,应引起临床重视.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的观察Roscovitine对TNF-α诱导的大鼠血管平滑肌细胞（VSMC）增殖及细胞周期的影响。方法组织贴块法培养大鼠VSMC细胞,采用TNF-α诱导其增殖,加入不同浓度的Roscovitine预处理15 h,将细胞分为:对照组、TNF-α组、Roscovitine 5、10、15、30μmol·L^-1组。MTT比色法检测细胞增殖活性;Western blot检测增殖细胞核抗原（PCNA）;流式细胞仪检测细胞周期;荧光定量RT-PCR及Western blot检测细胞周期蛋白（Cyclin A、Cyclin B、Cyclin D、Cyclin E）、细胞周期蛋白依赖激酶（CDK4、CDK5）、细胞周期抑制蛋白（p53、p21、p27）的表达。结果 Roscovitine能抑制VSMC增殖;抑制细胞周期从G₀/G₁期向S期转化。与TNF-α组比较,Roscovitine 5、10、15、30μmol·L^-1组能降低细胞周期蛋白Cyclin A、Cyclin B、Cyclin D、Cyclin E蛋白表达,降低细胞周期蛋白依赖激酶CDK4、CDK5蛋白表达,升高细胞周期抑制蛋白p53、p21、p27蛋白表达（P&lt;0.05）。结论 Roscovitine可抑制大鼠VSMC细胞周期进程及增殖活性。</span>

Objective To observe the concentration of endothelin-1 (ET-1), nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and expression of eNOS mRNA in plasma and myocardial tissue, and discuss the molecular biological mechanism of vascular endothelial system in rats with high-sodium diet. Methods SD rats (n=84) were divided randomly into high-sodium diet group (with oral 0.9% NaCL solution) and control group (with oral deionized water, each n=42). All groups were given adaptive feeding for 2 wk and experimental feeding for 8 wk. The concentration of ET-1, NO and eNOS and expression of eNOS mRNA in plasma and myocardial tissue were detected respectively. Results The level of serum sodium and plasma ET-1 concentration were significantly higher (P<0.05) and concentration of plasma eNOS and NO were significantly lower (P<0.05) in high-sodium diet group than those in control group. The concentration of NO and eNOS and eNOS mRNA expression in myocardial tissue were significantly lower (P<0.05), and ET-1 concentration in myocardial tissue was significantly higher (P<0.05) in high-sodium diet group than those in control group. Conclusion This study indicates further that high-sodium diet can induce atherosclerotic vascular lesions and target organ damage through influencing the function of vascular endothelial system.

骨质疏松症( osteoporosis )是一种常见的全身性、代谢性骨病,其特征为骨量减少和骨组织结构破坏,导致骨密度( bone mineral density,BMD)下降和脆性骨折的风险增加[ 1-2]. 在成年期,随着年龄的增长,骨量逐渐减少,所以骨质疏松症是公认的老年人常见疾病.骨质疏松症影响了全世界范围内三分之一的女性和八分之一50岁以上的男性[3].

目的:探讨roscovitine抑制大鼠血管平滑肌细胞(VSMC)炎症因子表达及对核因子-κB(NF-κB)通路的作用.方法:组织贴块法培养大鼠VSMC细胞,采用肿瘤坏死因子-α(TNF-α)诱导其增殖.将细胞分为对照组、TNF-α组、roscovitine 5,10,15和30 μmol·L-1组.四甲基氮唑蓝(MTT)法和细胞计数法检测细胞增殖;实时荧光定量PCR(qRT-PCR)和免疫印迹分析(Western Blot)检测NF-κB、NF-κB诱导激酶(NIK)、IkB激酶α(IKKα)、抑制性蛋白kBα(IkBα)表达.结果:Roscovitine可显著抑制VSMC增殖;与TNF-α组比较,roscovitine组p-NIK/NIK,p-IKKα/IKKα,p-IκBα/IκBα表达水平明显降低;p-NF-κB,核NF-κB,NF-κB表达水平明显降低(P＜0.05).结论:Roscovitine抑制VSMC炎症因子的表达与抑制NF-κB活性有关,可用于血管增生性疾病的防治.

Objective To investigate the effects of rosiglitazone (RSG) on the expressions of PGC-1 α and GLUT4 in skeletal muscles of aged rats fed by high-fat diets,and to observe the changes of insulin sensitivity.Methods The male Wistar rats aged 21 ～ 23 months were divided into three group:control group (n =20),high-fat diet group (HF group,n =20) and RSG intervention group (high-fat diet + RSG,n =20).At the end of the 8th week,the insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp technique.The expression levels of PGC-1 α and GLUT4 in skeletal muscle were detected by polymerase chain reaction (PCR) and Western Blot,respectively.Results As compared with those in control group,the serum levels of triacylglycerol and free fatty acids as well as the triglyceride levels in skeletal muscles in HF group were significantly increased at the end of the 8th,however,the glucose infusion rate in HF group was significantly decreased (P ＜0.05).As compared with those in HF group,the serum levels of triacylglycerol and free fatty acids as well as the triglyceride levels in skeletal muscles in RSG intervention group were significantly decreased at the end of the 8th,however,the glucose infusion rate in HF group was significantly increased (P ＜ 0.05).Moreover,as compared with those in control group,the expression levels of PGC-lα and GLUT4 in skeletal muscles in HF group were significantly decreased,however,the expression levels of PGC-1 α and GLUT4 in RSG intervention group were significantly higher than those in HF group,but,which were still significantly lower than those in control group (P ＜ 0.05).Conclusion The high-fat diet can induce insulin resistance of rats,with down-regulating of expresions of PGC-1 o and GLUT4 in skeletal muscles of aged rats fed by high-fat diet.Moreover RSG intervention can improve insulin resistance and increase the expressions of PGC-1 and GLUT4 in skeletal muscle.

目的:探讨roscovitine抑制大鼠血管平滑肌细胞(vascular smooth muscle cell,VSMC)增殖和信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)途径介导的作用机制.方法:组织块贴壁法培养大鼠VSMC,加入不同浓度的roscovitine预处理15 h后,应用肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)诱导其增殖,将细胞分为对照组、TNF-α组及5、10、15和30μmol/L roscovitine+TNF-α组.MTT法和活细胞计数法检测细胞活力和增殖;比色法检测细胞丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(super-oxide dismutase,SOD)的活性;real-time PCR及Western blot检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、细胞周期蛋白D1(cyclin D1)、细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)及STAT3表达的变化.结果:Roscovitine能抑制TNF-α诱导的VSMC增殖;降低MDA水平,升高SOD活性;抑制PCNA、cyclin D1和ICAM-1表达;阻断STAT3磷酸化活化及核转位.给予STAT3抑制剂WP1066能阻断roscovitine对VSMC增殖的抑制作用.结论:Roscovitine可通过STAT3途径抑制大鼠VSMC增殖.

Objective To investigate the effect of oxymatrine on hepatic lipid transport in insulin resistant of mice.Methods C57BL/6J mice were selected as control group.Apolipoprotein E gene knockout (ApoE-/-)mice were fed with high-fat diet for 16 weeks to establish the model of insulin resistance,which were randomly divided into model group,low,middle and high dose experimental groups.The experimental groups were given a gavage of 25,50,100 mg · kg-1 oxymatrine,respectively.All groups were continuously administrated for 8 weeks.Hyperinsulinemic-euglycemic clamp test were measured.The expression levels of lipid transport enzyme regulated genes in the hepatic were examined by real-time fluorescence quantitative PCR and Western-blot.Results Compared with the control group,the contents of triglyceride (TG),cholesterol (TC) and fatty acid (FFA) in the liver of model group significantly increased.Compared with the control group,serum fasting blood glucose (FBG),TC,TG and FFA levels significantly increased.Fasting insulin (FINS) were lower.Glucose infusion rate (GIR) (16.46 ± 1.62) mU · kg-1 · min-1 in model group was significantly lower than that control group.Lipoprotein lipase (LPL) and fatty acid translocase (FAT/CD36) mRNA expression in model group increased,which were 2.21 ±0.35 and 3.61 ±0.42.Carnitine palmitoyl transferase 1 (CPT1) and peroxisome proliferator-activated receptor α (PPARα) mRNA expression in model group decreased,which were 0.28 ±0.04 and 0.23 ±0.04.The protein expressions of LPL,FAT/CD36 (0.93 ±0.15,0.72 ±0.08) in model group increased,while CPT1,PPARα (0.31 ± 0.05,0.22 ± 0.04) in model group decreased.The differences in above factors were statistically significant (all P ＜ 0.05).After administration,the contents of TG,TC and FFA,blood lipid,insulin levels decreased in the liver of experimental group.The GIR values of middle and high dose experimental groups were 20.13 ± 1.84 and 21.33 ±2.26 respectively.LPL,FAT/CD36 expression were down -regulation,while CPT1,PPARa expression were up-regulation.The LPL mRNA expressions of middle and high dose experimental groups were 1.60 ±0.21 and 1.19 ±0.14 respectively,and the FAT/CD36 mRNA expressions were 1.63±0.19 and 1.78±0.24.CPT1 were0.87 ±0.12,0.90±0.15,and PPARα were0.68±0.11,0.55 ±0.08 respectively.The LPL protein expressions were 0.61 ± 0.08,0.45 ± 0.06,FAT/CD36 were 0.33 ± 0.04,0.36 ±0.05,CPT1 were 0.96 ±0.13,0.99 ±0.17 and PPARα were 0.65 ±0.10,0.71 ±0.11 respectively in the two groups.The differences of above indexes were statistically significant (all P ＜ 0.05).Conclusion Oxymatrine can adjust the lipid transport enzyme in hepatic,thus improving insulin resistance in mice.

AIM:To study the effect of roscovitine on the inflammatory hyperplasia of carotid artery intima in rats and the related mechanisms .METHODS: SD rats ( n=60 ) were randomly divided into 3 groups including control group, model group and treatment group .The rat model was established by trypsin digestion injury .The rats in control group were given sham operation .The rats in treatment group were administered with 0.5 mL roscovitine (2 g/L) slow-re-leasing gelatin.The rats in each group were fed normally for 4 weeks, then killed to take out carotid arteries for further ob-servations .The effects of roscovitine on the inflammatory hyperplasia of carotid artery intima and the related mechanism via nuclear factor-κB ( NF-κB) in the rats were detected by Western blot .RESUITS:Roscovitine inhibited the activation of NF-κB and the expression of inflammatory factors cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1),TNF-αand IL-6 via blocking the phosphorylation activation of NF-κB and inhibiting the degradation of IκB-α.CON-CLUSION:Roscovitine inhibits inflammatory hyperplasia of carotid artery intima in the rats via suppressing NF-κB activa-tion.

To observe metabolic abnormalities, histology changes and eNOS expression of aorta in type 2 diabetes rat.And to observe intervention effect of rosiglitazone.Methods 80 male Wistar rats were randomized to control group, high diet group, diabetes group, and rosiglitazone treatment group (diabetes plus rosiglitazone treatment).Type 2 diabetes models were developed and rosiglization group was treated with rosiglitazone .Six weeks and twelve weeks after treatment with rosiglitazone, blood glucose, endothlin and nitric oxide were tested.Histology changes of aorta in different groups were observed under microscopy .Meanwhile the protein and mRNA expression of eNOS in aorta were examined.Results 1)Compared with control group, ET in high fat diet group, diabetes group and rosiglitazone group increased significantly , and the level of NO decreased significantly at 6 week and 12 week.At 12 week, ET in diabetes group increased, and NO decreased significantly than that of high fat diet group and rosiglitazone group.2)Histology changes were observed in high fat diet group , diabetes group and rosiglitazone group at 12 week.3)Compared with control group, protein and mRNA expression in high fat diet group , diabetes group and rosiglitazone group were down regulated at 6 week and 12 week.And protein expression in diabetes group was down regulated than that in rosiglitazone group .Conclusions Rosiglization can ease the endothelial dysfunction in type 2 diabetes rat.

Objective:To investigate the effect of oxymatrine on hepatic inflammatory cytokines in fatinduced insulin resistance (IR) mice,and investigate the effect on c-Jun NH2-terminal kinase (JNK) pathway.Methods:ApoE-/-mice fed with high fat diet for 16 weeks were selected as IR animal model and randomly divided into the model group,oxymatrine 25,50,100 mg· kg-1 groups.C57BL/6J mice were selected as the normal control group.There were 10 mice in each group.The mice were gavage with oxymatrine for 8 weeks.Glucose tolerance test were conducted.Fasting blood glucose (FBG),cholesterol (TC),triglyceride (TG),fatty acid (FFA) and serum insulin (FINS) were detected.The expression levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1 β) in hepatic cells were examined by real-time PCR and western-blot.The p-JNK and JNK expression were examined by western-blot.Results:Oxymatrine reduced the levels of FBG,TG,TC,FFA and improved insulin resistance.Compared with the model group,the expression of IL-6 decreased in the oxymatrine 25 mg·kg-1 group.TNF-α,IL-6,IL-1β,p-JNK/JNK expression decreased in the oxymatrine 50,100 mg· kg-1 group.Conclusions:Oxymatrine inhibits inflammatory cytokines in hepatic cells by inhibiting JNK pathway,thus ameliorates fat-induced insulin resistance in mice.

OBJECTIVE:To investigate the molecular mechanism of arsenic trioxide(ATO) inhibiting K562 cell proliferation, and explore the new targets for treating chronic myeloid leukemia(CML).METHODS:human CML cell line K562 cells were cultured in vitro, and were treated with different concentrations of ATO; MTT was used to detect the cell proliferation; flow cytometry(FCM) was used to determine cell apoptosis, cell cycle and the expression of CD44; Transcriptional levels of β-catenin and cyclin D1 were assayed by RT-PCR.RESULTS:2 µmol/L ATO could inhibit the cell proliferation obviously in a time-and-dose-dependent manner. With drug concentration increasing and time prolonging, the expression rate of CD44 was declined gradrually. FCM with AnnexinV/PI double staining showed that K562 cells were induced to apoptosis after exposure to 2.5-10 µmol/L ATO for 48 hours and in dose-dependent manner. Treating with different concentration ATO for 48 hours, cell ratio of G0/G1 phase increased and cell ratio in S phase decreased gradually. RT-PCR showed that the expression of β-catenin and CyclinD1 decreased with increasing of drug concentration.CONCLUSION:ATO in certain concentration range can inhibit K562 cell proliferation, and induce the cell apotosis, the mechanismin influencing the Wnt/β-catenin pathway may be the downregulation of CD44 expression, arresting K562 cells in G0/G1 phase, and affecting the gene transcription, thus inhibiting K562 cell proliferation.

Objective To investigate the effects of oxymatrine on fatty acid oxidation in liver of high fat diet induced insulin resistance mice.Methods 72 ApoE-/-mice fed with high fat diet for 16 weeks to construct insulin resistance model were randomly divided into the model group and Oxymatrine 25,50,100 mg/kg groups,18 in each group.Eighteen C57BL/6J mice were recruited as the control group.Then the mice were administered with appropriate oxymatrine by gastrogavage for 8 weeks in each dose group of oxymatrine,equal volume of pure water to the control and model group.Hyper insulinemiceuglycemic clamp test was used to evaluate insulin resistance of mice,while the glucose infusion rate (GIR) was measured.The levels of free fatty acid (FFA) in the serum and hepatic tissues,FBG,TC,TG and FINS were detected,while the insulin resistance index (HOMA-IR) was calculated.The expression levels of fatty acid oxidation regulators [peroxisome proliferator-activated receptor α (PPARα),cvtochrome P4502E1 (CYP2E1),cytochrome P4504A1 (CYP4A10)],fatty acid oxidation rate-limiting enzyme [carnitine palmitoyl transferase 1 (CPT1),cytochrome oxidase (COX1) and solution uncoupling protein 2 (UCP2)] in liver tissues were examined by Real-time reverse transcription PCR (qRT-PCR) and Western blot.Results Compared with the control group,the body weight,serum FBG,TC,TG,FINS,HOMA-IR value,serum and liver FFA content increased significantly (P ＜0.05),while GIR decreased in the model group (P ＜0.05).The mRNA and protein expression levels of PPARα,CYP2A1,CYP4A10 and CPT1 decreased (P ＜0.05),while COX1 and UCP2 increased in the model group (P ＜0.05).Compared with the model group,the levels of TC,TG and HOMA-IR decreased in oxymatrine 25 mg/kg group (P ＜0.05),while the levels of FBG,TC,TG,FINS and HOMA-IR increased in oxymatrine 50 mg/kg group (P ＜0.05).The levels of weight,FBG,TC,TG,FINS and HOMA-IR decreased in oxymatrine 100 mg/kg group (P ＜0.05),while GIR increased in oxymatrine 50 and 100 mg/kg groups (P ＜0.05).Compared with the model group,the mRNA and protein expression levels of PPARα,CYP2E1,CYP4A10 and CPT1 increased in all oxymatrine groups (P ＜0.05),COX1 and UCP2 mRNA and protein expression decreased (P ＜0.05),while the contents of FFA in serum and liver decreased (P ＜0.05).Conclusion Oxymatrine can regulate the fatty acid oxidation in liver,thus improving high-fat induced insulin resistance in mice.

目的：探讨含钾通道四聚化结构域15（ KCTD15）基因 rs11084753位点多态性与石家庄市社区人群肥胖的相关性。方法应用2012～2013年河北省人民医院体检中心体检人群调查资料，对97588例18岁以上人群的超重、肥胖现状及影响因素进行流行病学分析。应用直接测序法对其中4500例人员（肥胖组人员3500例、对照组人员1000例）EDTA 抗凝血 KCTD15基因的多态性情况进行检测。结果体检人群中男性体重指数（BMI）（27.61±11.48）kg ／m2，女性 BMI（24.76±11.58）kg ／m2；男性腰围（WC）（88.57±16.47） cm，女性 WC（77.14±14.36） cm，女性 BMI 及WC 随年龄的增加而增大。男性 BMI 以35～44岁为最高，WC 以55～64岁为最高。超重、肥胖的现患率分别为41.97％和18.14％，男性（48.87％、22.10％）高于女性（33.84％、13.49％）（P＜0.05）。基因多态性分析显示，肥胖人群 KCTD15基因 rs11084753位点 GG 及 AG 基因型明显高于对照组（P＜0.05）；Logistic 回归分析显示，基因型是 BMI 的独立影响因素。结论石家庄市社区体检人群超重和肥胖发生率明显升高，这些人员肥胖超重与 KCTD15基因 rs11084753位点多态性有关。

AIM: To investigate the effect of oxymatrine ( OXY ) on high fat-induced insulin resistance in mice, and to investigate the mechanism. METHODS:ApoE-/ -mice with high-fat diet for 16 weeks were divided into in-sulin resistance group, and OXY groups at concentrations of 25, 50 and 100 mg/kg. C57BL/6J mice served as normal con-trol group. The mice in OXY groups were gavaged with OXY for 8 weeks. Glucose tolerance test in the mice was per-formed. Fasting blood glucose ( FBG) , total cholesterol ( TC) , triglyceride ( TG) , fatty acid ( FFA) and fasting insulin (FINS) in the plasma were measured. The mRNA expression of insulin receptor (INSR), insulin receptor substrate-2 (IRS-2), glucose transporter 2 (GLUT2) in the liver tissues was examined by RT-qPCR. The protein levels of GLUT2, INSR, IRS-2, p-INSR, p-IRS-2, PI3K, p-PI3K, serine/threonine protein kinase ( AKT) and p-AKT were examined by Western blot. RESULTS:OXY reduced the levels of FBG, TC, TG, FFA and FINS, and attenuated insulin resistance. Compared with insulin resistance group, the mRNA expression of INSR, IRS-2 and GLUT2 significantly increased in OXY groups (P<0. 05). The protein levels of p-INSR/INSR, p-IRS-2/IRS-2, p-PI3K/PI3K, p-AKT/AKT and GLUT2 also increased in OXY groups (P<0. 05). CONCLUSION:OXY ameliorates high fat-induced insulin resistance in mice via PI3K/AKT pathway.

目的 探讨氧化苦参碱(OXY)对高脂诱导IR ApoE-/-小鼠肝脏成纤维细胞因子-21(FGF-21)/β-klotho/FGF-21受体1(FGFR1)通路的作用. 方法 ApoE-/-小鼠分为模型(IR)组、氧化苦参碱25 mg/kg(IR+ 25OXY)组、氧化苦参碱50 mg/kg(IR+ 50OXY)组、氧化苦参碱100 mg/kg(IR+100OXY)组,C57BL/6J小鼠作为对照(NC)组.计算HOMA-IR和ISI.QRT-PCR和Western blot检测肝组织FGF-21、β-klotho蛋白(pklotho)、FGFR1表达. 结果 与IR组比较,IR+ 50OXY组和IR+100OXY组HOMA-IR值降低(31.54±4.30)vs(21.84±1.87)vs(17.27±3.59)],ISI值升高[(0.022±0.000)vs (0.034±0.010) vs (0.042±0.010)] (P＜0.05);OXY可使FGF-21、β-klotho、FGFR1mRNA和蛋白表达有不同程度的降低. 结论 OXY能通过调节肝脏FGF-21/pklotho/FGFR1通路,改善高脂诱导小鼠的IR.

Objective To investigate the effect of oxymatrine on genes regulated hepatic cholesterol metabolism in ApoE - / - mice induced by high fat diet. Methods From April 2014 to January 2015,seventeen SPF grade C57BL/ 6J mice were selected as normal control(NC)group and fed on the basal diet. Sixty - eight SPF grade ApoE - / - mice fed on high fat diet. After 16 weeks of feeding,according to the random number table method,ApoE - / - mice were averagely divided into insulin resistance&nbsp;model group(IR group),low oxymatrine dose group(OXYL group),middle oxymatrine dose group(OXYM group)and high oxymatrine dose group(OXYH group). There were seventeen mice in each group. In OXYL group,OXYM group and OXYH group,25 mg·kg - 1 ·d - 1 ,50 mg·kg - 1 ·d - 1 and 100 mg·kg - 1 ·d - 1 oxymatrine were given by continuous oral gavage for 8 weeks,and all groups were given equal volume of pure water. Glucose infusion rate(GIR),blood glucose(FBG)level,serum leves of total cholesterol( TC),three glycerol( TG),low density lipoprotein cholesterol( LDL-C),high density lipoprotein cholesterol(HDL-C),fasting insulin( FINS)level in each group of mice were measured,and the insulin resistance index (HOMA - IR)was calculated,and the TC level of liver tissue was detected. The expression of SREBP-2,SCAP,INSIG2, HMGCR and LDLr mRNA and its protein were detected using RT - qPCR and western - blotting methods in mice liver tissue. Results The FBG level,serum levels of TC,TG,LDL-C and HDL-C in IR group was significantly higher than NC group (P < 0. 05). The serum levels of TC,TG,LDL-C and HDL-C in OXYL group was significantly lower than IR group( P <0. 05). The FBG level,serum levels of TC,TG,LDL-C and HDL-C of in OXYM and OXYH group were significantly lower than IR group(P < 0. 05). GIR in IR group was lower than NC group(P < 0. 05);GIR in OXYL group,OXYH group and OXYM group was higher than IR group(P < 0. 05);The FINS level and HOMA - IR in IR group were higher than NC group (P < 0. 05). The HOMA - IR in OXYL group was lower than IR group(P < 0. 05). The FINS level,HOMA - IR in OXYH group and OXYM group were lower than IR group(P < 0. 05). The TC level in mice liver tissue of IR group was higher than NC group(P < 0. 05). The TC level in mice liver tissue of OXYL group,OXYM group and OXYH group was lower than IR group (P < 0. 05). The expressions of SREBP-2,HMGCR,LDLr mRNA and their protein in mice liver tissue of IR group were lower than NC group,and the expressions of SCAP,INSIG2 mRNA and their protein in mice liver tissue of IR group were higher than NC group(P < 0. 05). The expression of LDLr mRNA and its protein in mice liver tissue of OXYL group were higher than IR group(P < 0. 05). The expressions of SREBP-2,HMGCR,LDLr mRNA and their protein in mice liver tissue of OXYH group and OXYM group were higher than IR group,and the expressions of SCAP,INSIG2 mRNA and their protein in mice liver tissue of OXYH group and OXYM group were lower than IR group(P < 0. 05). Conclusion Oxymatrine could regulate the expression of genes related hepatic cholesterol and improve the blood glucose,lipid and insulin resistance in ApoE - / - mice induced by high fat diet.

Objective To investigate the changes of early islet function and glucose-regulated protein78 (GRP78) of insulin resistance rats induced by high-fructose feeding. Methods A total of 36 male Wistar rats were randomly divided into control group (n=18) and high-fructose feeding group (n=18), and were fed with common diet and high-fructose di-et respectively for 8 weeks. The related indexes were detected, and islet function was evaluated by calculating values of ho-meostasis model assessment insulin resistance ( HOMA-IR) , HOMA-βand△I30/△G30 using oral glucose tolerance test ( OGTT) in rats. The GRP78 protein levels were detected by isolating and purifying islets of the rats. Results Compared with those in control group, in high-fructose group, levels of fasting serum insulin, proinsulin, triglyceride ( TG) and HO-MA-IR and islet GRP78 protein expression were significantly higher (P<0. 01),△I30/△G30 value (reflecting the early phase insulin secretion function) was significantly lower (P<0. 01), but no significant difference was observed for HOMA-β( P>0. 01 ) . Conclusion The high-fructose feeding for 8 weeks can induce early islet dysfunction and can increase GRP78 protein expression in rats, and islet dysfunction may relate to endoplasmic reticulum stress.