自发性糖尿病大鼠肾脏微血管密度的实验研究

目的 观察自发性糖尿病大鼠(Goto-Kakisaki Rats, GK)肾脏微血管在糖尿病的不同发展时期的变化规律,为糖尿病肾病的血流灌注研究提供实验基础。方法 选取雄性GK大鼠和Wistar大鼠各30只,每种按周龄分组(4、12、20周各10只)。肾脏标本常规石蜡包埋切片后,用免疫组化法染色。每只肾脏标本取切片5张,每张切片皮质区、髓质区各随机观察18个视野。采用图像分析系统定量分析微血管密度。每张切片随机选取5个肾小球,采用不规则方式分割,分析其周长、面积、毛细血管密度。结果(1) GK各周龄组髓质微血管密度均小于对照组(P<0.05～P<0.01),GK组间有差异(P<0.01)。(2) GK 20周龄组肾小球微血管密度明显小于同周龄Wistar组(P<0.01)。GK组间、对照组间均存在差异(P<0.01～P<0.05)。(3) GK4周龄组肾小球平均周长明显大于同周龄Wistar(P=0.01)。不同周龄Wistar组间亦有差异(P<0.01～P<0.05)。结论 GK大鼠存在肾微血管稀少的现象,有可能是糖尿病的继发性改变之一;低周龄GK大鼠肾髓质微血管稀少可能与遗传有关。     

当归补血汤主要吸收成分对GK大鼠肾保护作用研究

〖H观察当归补血汤主要吸收成分对2型糖尿病模型GK大鼠肾保护作用及可能机制。方法 UPLCMS/MS定性定量吸收入血活性成分(ABCs),确定ABCs组成,定量1g母方中ABCs浓度。GK大鼠按血糖随机分为模型组、当归补血汤组及吸收成分（ABCs）组,每组10只,给药组分别灌胃当归补血汤（4g/kg）、吸收入血的生物活性成分（剂量相当于母方含量,即咖啡酸5.36mg/kg,芒柄花素2.68mg/kg,毛蕊异黄酮2.56mg/kg,阿魏酸1.36mg/kg,黄芪甲苷0.45mg/kg,丁苯酞0.16mg/kg,蒿本内酯0.16mg/kg）,10只普通Wistar大鼠作为空白对照,给予等量生理盐水,每日1次,连续给药28d。观察指标:①肾脏系数、尿总蛋白和尿白蛋白;②肾组织氧化应激;③病理切片观察肾脏组织形态。结果 当归补血汤及ABCs均能够改善糖尿病大鼠的肾脏肥大,显著降低糖尿病模型大鼠尿总蛋白、尿白蛋白和肾脏MDA水平（P<0.05）,显著升高肾脏总SOD活力（P<0.05）,且对肾脏组织病理形态学有保护作用;与当归补血汤组比较,ABCs作用不如汤剂显著。结论 ABCs能够代表母方当归补血汤发挥对GK大鼠的肾保护作用,机制涉及氧化应激。母方中除ABCs外,其微量元素、氨基酸、多糖等其他成分也同时发挥着药效作用。     

The correlations among racial/ethnic groups,hypertriglyceridemia, thrombosis,and mortality in hospitalized patients with COVID-19

Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. Our previous study has shown that patients with COVID-19 who developed hypertriglyceridemia during hospitalization have a 2.3 times higher mortality rate. However, whether the correlation between hypertriglyceridemia and mortality has disparity among different racial and ethnic groups is unknown.In this study, we investigated the impact of race/ethnicity on the correlation between hypertriglyceridemia and mortality in hospitalized patients with COVID-19. De-identified information from 904 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted from the Medical College of Wisconsin Clinical Data Warehouse. A multivariable regression analysis suggested that the Asians and non-White Hispanics had 4 or 3.9 times higher mortality rate, respectively, after adjusting for age, morbid obesity (BMI ≥40), and gender. The hypertriglyceridemia (≥150 mg/dL) was associated with higher mortality, after adjusting for age, gender, and morbid obesity. The baseline hypertriglyceridemia occurrence had relevantly more consistent percentages among all racial/ethnic groups. However, non-White Hispanic and Asian patients had the highest frequencies of peak hypertriglyceridemia occurrence during hospitalization. The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombosis after adjusting for morbid obesity, age, and sex. In summary, in this retrospective study of 904 hospitalized COVID-19 patients, Asians and non-White Hispanics had a greater likelihood of developing hypertriglyceridemia during hospitalization and mortality than White patients.     

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.     

参芪复方对GK大鼠白色脂肪组织脂联素基因表达的影响

目的:探讨参芪复方抗2型糖尿病低度炎症的作用机理。方法:SPF级GK大鼠按血糖水平随机分为模型、雷米普利、参芪复方低剂量与参芪复方高剂量组,另设正常Wistar对照组。4组GK大鼠和正常Wistar对照组分别腹腔注射L-N-硝基精氨酸甲酯(N-ω-nitro-L-arginine methyl ester,L-NAME)和生理盐水,同时喂饲高脂饲料和普通饲料。各组动物每天灌胃相应受试物和无菌水32 d。酶免法检测血清C反应蛋白(C reactive protein,CRP)和脂联素含量,实时定量RT-PCR法检测脂肪脂联素mRNA表达。结果:参芪复方低、高剂量组大鼠的血清CRP水平较模型组显著降低(P<0.01),脂联素mRNA表达和血清蛋白含量较模型组明显增加(P<0.05或P<0.01)。结论:提高脂联素mRNA表达和血清蛋白水平可能是参芪复方抗T2DM低度炎症的作用机制之一。     

GK糖尿病大鼠生物学特性观察

目的了解2型糖尿病模型GK大鼠生长曲线、主要脏器重量、糖代谢等生物学特性,评价GK大鼠葡萄糖刺激的胰岛素分泌能力。方法采用51只雄性GK大鼠及15只年龄性别匹配的Wistar大鼠作为研究对象。测定13周龄GK、Wistar大鼠空腹血糖、23周龄GK大鼠空腹及随机血糖。随访GK及Wistar大鼠生长曲线,34~46周龄期间血糖、糖化血红蛋白。46周龄时行腹腔葡萄糖耐量实验(IPGTT),计算相关参数评价β细胞葡萄糖刺激的胰岛素分泌能力;之后处死大鼠,脏器称重。比较GK及Wistar大鼠间上述各指标差异。结果13周龄GK大鼠空腹血糖4.74±0.41 mmol/L,对照Wistar大鼠1.85±0.44 mmol/L(P<0.001)。23周龄GK大鼠空腹血糖7.88±1.96mmol/L,随机血糖9.91±3.52~13.46±4.13 mmol/L。7~20及34~45周龄期间GK大鼠体重高于对照Wistar大鼠(P<0.05),46周龄时无显著性差异。34~45周龄期间GK大鼠空腹血糖、进食后血糖、HbA1c均高于对照Wistar大鼠(P<0.05)。IPGTT曲线下面积分析示GK大鼠胰岛素曲线下面积(AUCi)、葡萄糖曲线下面积(AUCg)高于对照Wistar大鼠,胰岛素与葡萄糖曲线下面积比值(AUCi/AUCg)低于对照Wistar大鼠,差异均有显著性(P<0.05)。GK大鼠肾脏重量高于对照Wistar大鼠(P<0.05),余主要脏器重量差异无显著性。结论GK大鼠空腹血糖、进食后血糖、HbA1c水平升高,葡萄糖刺激的胰岛素分泌能力(GSIS)减退,葡萄糖刺激后胰岛素分泌早期相消失,晚期相代偿性增加,具有2型糖尿病特点;体重、血糖等生物学特性稳定。     

参芪复方对GK大鼠心肌细胞凋亡相关因子Bcl-2、Bax及NO的影响

[目的]研究参芪复方对GK大鼠心肌细胞凋亡相关因子Bcl-2、Bax及一氧化氮(NO)的影响及其可能作用机制.[方法]GK大鼠腹腔注射N-硝基-L-精氨酸甲酯(L-NAME),同时给予高脂饮食复制2型糖尿病(T2DM)心肌病变模型.选择随机血糖≥11.1 mmol/L的GK大鼠随机分为4组:模型组、中药高、低剂量组、西药组,另设正常Wistar大鼠作正常对照组,共5组动物.治疗4周后,统一取心肌标本,通过免疫组化等测量方法,对照观察各组药物对GK大鼠一般状态、心肌NO、心肌Bcl-2、Bax蛋白表达的影响.[结果] GK大鼠的上述指标存在明显异常.参芪复方特别是其高剂量组能改善其一般状态、升高心肌NO(P<0.01),升高心肌细胞凋亡抑制因子Bcl-2的表达(P<0.01),降低促细胞凋亡因子Bax表达(P<0.05)和Bax/Bcl-2比值(P相似文献   

Animal models to test drugs with potential antidiabetic activity

Although medicinal plants have been historically used for diabetes treatment throughout the world, few of them have been validated by scientific criteria. Recently, a large diversity of animal models has been developed to better understand the pathogenesis of diabetes mellitus and new drugs have been introduced in the market to treat this disease. The aim of this work was to review the available animal models of diabetes and some in vitro models which have been used as tools to investigate the mechanism of action of drugs with potential antidiabetic properties. In addition, a MEDLINE/PUBMED search for articles on natural products, pancreatectomy and diabetes mellitus treatment published between 1996 and 2006 was done. In the majority of the studies, natural products mainly derived from plants have been tested in diabetes models induced by chemical agents. This review contributes to the researcher in the ethnopharmacology field to designs new strategies for the development of novel drugs to treat this serious condition that constitutes a global public health.     

骨髓间充质干细胞对糖尿病周围神经病变大鼠骨组织OGP/RANKL表达的影响

目的检测骨髓间充质干细胞局部注射后糖尿病周围神经病变大鼠骨组织OPG/RANKL的表达水平。方法 8周龄SPF级雄性自发性2型糖尿病GK大鼠30只,高脂饲料喂养造模。造模成功后(随机血糖≥11.1 mmol/L)暴露大鼠左侧股骨,人为造成开放性骨折并给予克氏针复位内固定,将培养收集浓缩的骨髓间充质干细胞注射于骨折周围肌肉软组织,于实验后第12周、16周、20周分别取材用免疫组化、western blot测定骨质OPG、RANKL的表达。结果实验组大鼠术后第12周、16周、20周骨组织免疫组化和western blot测定OPG表达明显较对照组增高,而RANKL的表达结果正好相反。结论骨髓间充质干细胞局部移植可以促进GK糖尿病大鼠骨折后骨组织中OPG的高表达,抑制RANKL表达,从而促进糖尿病大鼠骨折后骨质的愈合。