Investigation of hypoglycemic,hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

Objective

To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats.

Methods

Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats.

Results

Oral administration of AETPB did not exhibit toxicity and death at a dose of 2 000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats.

Conclusions

Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition.     

Acute and subacute oral toxicity study on the flavonoid rich fraction of Monodora tenuifolia seed in albino rats

Objective

To investigate the effects of the flavonoid rich fraction of Monodora tenuifolia seed on the haematology, histopathology and liver profile of Wistar albino rats.

Methods

Toxicity study was investigated on the flavonoid rich fraction of Monodora tenuifolia in rats administered different concentrations orally for 28 d using standard laboratory procedures.

Results

The LD₅₀ of the flavonoid rich fraction was found to be above 5 000 mg/kg body weight in mice observed for 48 h. After the Day 14, biochemical markers of liver injury such as serum alanine aminotransferase, and aspartate aminotransferase decreased significantly (P<0.05 at doses of 100 and 200 mg/kg body weight and P<0.01 at 400 mg/kg) while serum alkaline phosphatase increased non-significantly (P>0.05). There was non-significant (P>0.05) effect observed across the groups in the levels of serum total protein, albumin, globulin, urea and creatinine. The result of histological examination showed various degrees of peribiliary hepatitis after the Day 14 which fizzled out after the Day 28.

Conclusions

The result therefore suggests that the seed extract is potentially safe.     

复方降压1号对两肾一夹大鼠的降压作用及其毒性

目的:研究复方降压1号口服给药对两肾一夹大鼠的降压作用及毒性。方法:采用两肾一夹(2K1C)法复制肾血管性高血压大鼠模型,取32只造模成功的大鼠随机分为复方降压1号高低剂量(0.6g/kg、0.2g/kg)组、尼群地平(0.001g/kg)组和模型对照组(蒸馏水5ml/kg),另设假手术组(蒸馏水5ml/kg)。按上述设定剂量每日灌胃给药1次,连续4周,每周测量血压和体重,4周后测定血脂、右肾湿重、肾功能和尿酸含量。采用分组法测定小鼠口服半数致死量(LD50)。结果:复方降压1号高低剂量组和尼群地平阳性组大鼠血压明显降低(P<0.05或P<0.01),其高剂量组降压作用较尼群地平组强(P<0.05),而对血脂、肾功能、尿酸和右肾湿重及其系数无明显影响。小鼠灌胃给药的LD50为18.066g/kg,按体重和动物系数计算约为成人量的643倍和72倍。结论:复方降压1号能明显降低两肾一夹大鼠的血压,其高剂量组降压效果强于尼群地平,对血脂、肾功能和尿酸无明显影响;其小鼠口服毒性较小。     

三种黎药的急性毒性研究

目的:观察辣蓼、薜荔和三叉苦等三种黎药水提物的急性毒性反应。方法:三种黎药水提物对小鼠进行灌胃给药,观察并记录小鼠急性毒性反应和死亡率,采用改良寇氏法测半数致死量LD50。结果:测得辣蓼LD50为128.3g.kg-1(相当于成人一次用量的256.6倍),LD5095%可信限为(111.1～139.7)g.kg-1,10d后存活小鼠体重平均增加22.2%。以最大给药量灌胃薜荔(213.6g.kg-1)和三叉苦(168.0g.kg-1),小鼠无死亡,12d后平均体重分别增加28.3%、28.5%。结论:薜荔和三叉苦口服无毒,而辣蓼毒性很小。     

氯沙坦对大鼠内毒素性急性肺损伤的影响及可能机制

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂氯沙坦在大鼠内毒素性急性肺损伤(ALI)中的保护作用及可能机制。方法将50只雄性Wistar大鼠随机分为4组:对照组、脂多糖(LPS)组、LPS+氯沙坦组和LPS+氯沙坦+A779组。制备麻醉状态下静脉注射LPS致大鼠ALI模型,并予氯沙坦或血管紧张素1-7[Ang(1-7)]拮抗剂A779干预。前3组均于注射后1、4、6 h进行观察,后1组于4 h观察,每个时间点观察5只大鼠。BCA法测定肺泡灌洗液和血清蛋白量,苏木素-伊红(HE)对右肺中叶病理染色并评分,ELISA法检测血清AngⅡ、Ang(1-7)变化。结果光镜下可见大鼠出现特征性ALI病理改变。与对照组相比,LPS组血清AngⅡ含量1 h、4 h时升高(P<0.01),血清Ang(1-7)含量1 h时降低、4 h时升高(P均<0.01)。与LPS组相比,LPS+氯沙坦组大鼠肺损伤程度减轻,病理评分下降(P<0.01)。结论氯沙坦主要通过调节Ang(1-7)水平对大鼠内毒素性ALI起保护作用。     

环孢素对心脏移植大鼠急性排斥反应及血清IDO活性的影响

目的 探讨不同剂量的强效免疫抑制剂环孢素（CsA）对同种异基因心脏移植大鼠急性排斥反应程度和血清吲哚胺2,3双加氧酶（IDO）活性的影响.方法 分别以SD和Wistar大鼠为供、受体,建立同种异基因大鼠颈部异位心脏移植模型.18只受体大鼠随机分为对照组、低剂量CsA组（CsA 2 mg·kg-1·d-1）和高剂量CsA组（CsA 15 mg·kg-1·d-1）,每组6只.术后第7天,所有受体大鼠经腹主动脉采集血样后处死,取移植心脏制备组织学检查标本.ELISA法检测血清白介素2（IL-2）和γ干扰素（IFN-γ）水平;高压液相色谱法检测血清犬尿氨酸和色氨酸浓度,计算两者比值并以此估算IDO活性.移植心脏标本常规HE染色,采用Stanford标准进行急性排斥反应程度分级.结果 三组血清IL-2和IFN-γ水平以及IDO活性比较显示,对照组＞低剂量CsA组＞高剂量CsA组,差异均有统计学意义（P＜0.05或P＜0.01）.三组移植心脏急性排斥反应程度分级结果显示,对照组＞低剂量CsA组＞高剂量CsA组,差异均有统计学意义（P＜0.01）.结论 CsA可明显减轻同种异基因大鼠移植心脏急性排斥反应程度并降低血清IDO活性,两者变化趋势一致且与CsA的使用剂量有关.提示血清IDO活性监测有可能成为一种无创性移植器官急性排斥反应及其程度的预测和评估方法.     

硫辛酸对急性冠脉综合征患者血清乙醛脱氢酶2活性、8-异前列腺素F2a含量的影响

目的 探讨硫辛酸(LA)对急性冠脉综合征(ACS)患者的心肌保护作用及可能机制。方法 选择ACS患者63例,分为硫辛酸组33例和常规药物组30例,硫辛酸组给予常规药物+硫辛酸治疗,常规药物组给予常规药物治疗,疗程1周。用药前(0h)、24h、1周抽取空腹静脉血,分别通过比色法、双抗体夹心ABC-ELISA法和免疫散色比浊法测定乙醛脱氢酶2(ALDH2)活性、8-异前列腺素F2a(8-iso PGF2a)及高敏C反应蛋白(hs-CRP)含量并进行分析。结果 治疗24h后,两组患者ALDH2活性水平显著上升(P<0．001), 8-iso PGF2a含量显著下降(P<0．001);硫辛酸组ALDH2活性升高(P<0.01),8-iso PGF2a含量下降较常规药物组更为明显(P<0．05);治疗1周后,两组ALDH2活性水平较0h明显上升(P<0．001),8-iso PGF2a含量较0h、24h均显著下降(P<0．001),hs-CRP含量较0h明显下降(P<0．001),硫辛酸组ALDH2活性、8-iso PGF2a、hs-CRP含量的变化较常规药物组更为明显(P<0.05)。结论 硫辛酸可以通过上调ALDH2活性、下调8-iso-PGF2a、hs-CRP的含量,抑制氧化应激及炎症反应而产生心肌保护作用。     

肺纤方提取物对肺间质纤维化大鼠肺微血管VEGF、VEGFR2、PAI-1、VCAM-1mRNA表达的影响

目的通过观察肺纤方提取物干预体外培养肺微血管的血管内皮细胞生长因子(VEGF)、血管内皮细胞生长因子受体2(VEGFR 2)、纤溶酶原激活物抑制物1(PAI-1)、血管细胞黏附因子1(VCAM-1)基因表达的影响,探讨肺纤方干预肺纤维化微血管生成的机制。方法从肺纤维化模型大鼠分离培养肺微血管内皮细胞,将其等量分为模型组,氯沙坦组,泼尼松组,肺纤方大、中、小剂量组。模型组加入含20%胎牛血清的DMEM培养基,氯沙坦组加入含20%胎牛血清及10 mg/L氯沙坦的DMEM培养基,泼尼松组加入含20%胎牛血清及5 mg/L泼尼松的DMEM培养基,肺纤方大、中、小剂量组分别加入含20%胎牛血清及100、60、20 mg/L肺纤方提取物的DMEM培养基,分别作用24 h。双链嵌合荧光染料SYBR GreenⅠ实时荧光定量PCR法检测VEGF、VEGFR 2、PAI-1与VCAM-1的mRNA转录水平。结果与模型组比较,肺纤方大、中、小剂量组VEGF基因表达水平均显著降低,而VEGFR2无显著差异;肺纤方大剂量组PAI-1 mRNA表达显著降低;肺纤方大、中剂量组VCAM-1 mRNA表达显著降低(P0.05)。结论肺纤方可通过抑制肺微血管VEGF、PAI-1及VCAM-1的表达改善血凝及纤溶,抑制血管形成而发挥抗肺纤维化作用。