实验性糖尿病大鼠肝,肾,心,脑脂肪酸代谢的动态变化

报道对链脲佐菌素（STZ）诱导的实验性糖尿病大鼠几种重要脏器（肝、肾、心、脑）卵磷脂、脑磷脂中脂肪酸构成的变化。不饱和脂肪酸变化的模式（C18：2n-6，C20：3n-6，C22：5n-3，C22：6n-3增加，C20：4n-6降低）基本相同，改变的先后顺序是肝→心、肾→脑。     

糖尿病引发股骨头缺血性坏死骨代谢的变化

目的:通过观察糖尿病引发股骨头缺血性坏死大鼠的骨代谢变化特征,分析其在糖尿病性股骨头缺血坏死发病过程中的作用.方法:采用腹腔内1次注射60mg/kg体重链脲佐菌素(STZ)的方法,建立速发型STZ-DM模型,进行相关骨代谢指标的测定.结果:实验组大鼠股骨头软骨下骨小梁稀疏、断裂,空缺骨陷窝显著增多;股骨头压缩强度明显降低;骨Ca、HOP含量及Ca/HOP比值均有显著降低;血清BGP、血Ca及钙磷乘积显著下降;尿Ca、P、HOP排泄量均有显著增多;结论:糖尿病存在骨代谢紊乱,引发骨质疏松,股骨头因应力作用引起软骨下骨压缩塌陷,压迫骨内微血管而继发缺血坏死.     

桑椹乙酸乙酯萃取物对链脲佐菌素致高血糖大鼠的降血糖作用

目的 研究桑椹乙酸乙酯萃取物(EEM)对链脲佐菌素(STZ)诱导的糖尿病大鼠的降糖作用.方法 用STZ诱导出1型糖尿病大鼠模型分成5组,分别用水、格列苯脲和0.1、0.2、0.3g/kg EEM连续灌胃3周,每周测定血糖.结果 与模型对照组相比,0.2 g/kg EEM能显著降低糖尿病大鼠血糖、糖化血清蛋白,刺激胰岛素分泌,增加体质量,调节血脂,增强机体抗氧化能力,同时具有一定的保护肾脏的功能,但对肝脏有一定副作用.结论 EEM能有效的控制糖尿病大鼠血糖水平,一定程度改善糖脂代谢紊乱.     

玉米须水提物对2型糖尿病大鼠糖-脂代谢及氧化应激的影响

目的探讨玉米须水提物对2型糖尿病大鼠糖-脂代谢及氧化应激状态的影响。方法将雄性Sprague-Dawley大鼠随机分为正常对照组、模型对照组、阳性对照组(二甲双胍)及玉米须水提物低、中、高剂量组,除正常对照组外,其余各组采用高脂高糖饲养加小剂量链脲佐菌素(STZ)诱导2型糖尿病大鼠模型。各组大鼠给药干预8周后,采用全自动生化仪检测空腹血糖(FBG)、三酰甘油(TG)、血总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的水平;紫外可见分光光度计测定血清游离脂肪酸(FFA)、丙二醛(MDA)和超氧化物歧化酶(SOD)的水平。结果玉米须水提物干预后,其中中、高剂量组可显著降低大鼠血清FBG、FFA、TG和TC的水平(P0.05或P0.01),且呈剂量依赖型,高剂量组显著降低血清LDL-C的水平(P0.05);同时,玉米须水提物各剂量组可显著降低大鼠血清MDA的含量,明显升高血清SOD的活性(P0.05或P0.01)。结论玉米须水提物可改善糖尿病大鼠糖-脂代谢,抑制氧化应激反应,对2型糖尿病大鼠产生保护作用。     

Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics

Ethnopharmacological relevance

Traditional Chinese medical herbs have been used in China for a long time to treat different diseases. Based on traditional Chinese medicine (TCM) principle, Chaihuang-Yishen granule (CHYS) was developed and has been employed clinically to treat chronic kidney disease including diabetic nephropathy (DN). The present study was designed to investigate its mechanism of action in treatment of DN.

Materials and methods

Diabetic rats were established by having a right uninephrectomy plus a single intraperitoneal injection of STZ. Rats were divided into four groups of sham, diabetes, diabetes with CHYS and diabetes with fosinopril. CHYS and fosinopril were given to rats by gavage for 20 weeks. Samples from blood, urine and kidney were collected for biochemical, histological, immunohistochemical and molecular analyses.

Results

Rats treated with CHYS showed reduced 24 h urinary protein excretion, decreased serum TC and TG levels, but CHYS treatment did not affect blood glucose level. Glomerular mesangial expansion and tubulointerstitial fibrosis in diabetic rats were significantly alleviated by CHYS treatment. Moreover, CHYS administration markedly reduced mRNA levels of NF-κB p65 and TGF-β1, as well as decreased protein levels of NF-κB p65, MCP-1, TNF-α and TGF-β1 in the kidney of diabetic rats.

Conclusions

CHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling.     

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.     

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.     

Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats

Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na⁺-K⁺-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-β, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.     

2型糖尿病大鼠模型制备实验研究

目的 探究建立2型糖尿病大鼠模型的主要影响因素,为制备2型糖尿病大鼠动物模型提供方法 参考.方法根据不同的高糖高脂饲料(HDF)配方、喂养周期及STZ注射剂量(35 mg/kg和40 mg/kg),将90只雄性SD大鼠随机分为正常对照组(NC组)及8个模型组(A-H组),每组各10只.STZ注射5 d后检测各组大鼠空腹血糖(FBG),首次空腹血糖测定后各组大鼠眼眶采血测定血清中总三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及空腹血清胰岛素(FINS)水平.第8周处死大鼠取肝脏、肾脏、脾脏、胰腺,称质量并计算脏器系数.结果 与正常对照组比较,各模型组的血糖值显著升高(P<0.01),TG、TC及LDL-C水平和肝、肾、胰腺等脏器系数都有不同程度升高且胰岛素敏感指数显著降低(P<0.05,P<0.01),成功建立2型糖尿病大鼠模型;大鼠注射STZ 35 mg/kg较40 mg/kg存活率大、存活时间长,血糖值差异无统计学意义(P>0.05);喂养周期为8周后注射STZ的大鼠较4周大鼠死亡率高.结论 HDF喂养4周后注射35 mg/kg STZ是建立2型糖尿病大鼠模型的较合适方法.     

通络益肾汤对链脲佐菌素DN大鼠疗效的实验研究

目的 观察通络益肾汤对链脲佐菌素（STZ）糖尿病肾病大鼠的疗效。方法采用STZ糖尿病肾病大鼠模型，分为正常组、病理组、通络益肾汤治疗组、西药治疗组（糖适平＋洛汀新）。观察各组大鼠治疗前后的一般状况、血糖、肾功（BUN、Scr）、肾脏病理等指标的变化。结果与病理组比较，通络益肾汤治疗组大鼠一般状况改善较好，血糖明显下降（P＜0．05），血清BUN、Scr显著降低（P＜0．01）。通络益肾汤治疗组与西药组比较，各项指标无明显差异。结论通络益肾汤能延缓糖尿病肾病的病理进展，对糖尿病肾病有确切的治疗效果。