急性高尿酸血症大鼠的红细胞血液流变学研究

高尿酸血症是多种疾病的危险因素,但人们对急性高尿酸血症的认识还存在不足。本研究旨在从血液流变学角度探讨急性高尿酸血症对红细胞的影响,为其临床处理提供参考依据。通过对大鼠灌胃500mg/kg的次黄嘌呤,同时腹腔注射100mg/kg氧嗪酸钾诱导短期急性高尿酸血症模型,在给药的第0、1、2、3、6h内眦取血测量血尿酸水平、红细胞的流变学指标和血浆丙二醛水平。结果表明给药后1、2、3h大鼠血尿酸水平显著升高,同期内红细胞的积分变形指数、松弛指数显著升高,红细胞的破碎率显著降低,给药后2h血浆丙二醛水平显著降低。结果提示,短期急性尿酸升高引起了红细胞流变学特性的改善和脂质过氧化水平的下降。     

高尿酸血症动物模型研究进展

构建合理的动物模型是研究高尿酸血症致病机制的重要环节.目前高尿酸血症动物模型复制方法多样,常用的造模动物为禽类和啮齿类,主要造模方法有补充尿酸前体物质次黄嘌呤、补充外源性尿酸,使用氧嗪酸抑制尿酸酶活性、腺嘌呤抑制尿酸排泄.相对成熟的造模方法为尿酸和氧嗪酸联合使用.高尿酸血症动物模型尚缺乏公认评价指标,理想的模型仍需进一...     

鹅肌肽降低高尿酸小鼠尿酸

目的探讨在实验性高尿酸小鼠模型中鹅肌肽对高尿酸的缓解作用,以及对肾功能相关指标的影响。方法采用酵母膏联合氧嗪酸钾及腺嘌呤的方法建立模型,4周之后采集血清、尿液、肾脏等标本,检测血尿酸、肌酐、尿素氮及尿酸清除率等指标。利用HE染色的方法观察肾脏形态学上的变化情。结果成功建立实验性高尿酸小鼠模型,鹅肌肽对高尿酸小鼠的干预后,其中血尿酸明显降低,尿酸清除率升高,而且具有浓度依赖性。结论鹅肌肽主要通过促进尿酸排泄,缓解高尿酸血症的作用。     

无症状高尿酸血症大鼠血液流变学和氧化应激的研究

目的 从血液流变学的角度对长期无症状高尿酸血症开展系统研究,为该症的临床处理提供参考依据。方法 将20只SD大鼠随机平均分为空白对照组和模型组。通过对大鼠腹腔注射250 mg/(kg?d)氧嗪酸钾诱导8周无症状高尿酸血症模型,采血测量尿酸水平、血液流变学指标、氧化和抗氧化指标。结果 模型组大鼠红细胞的聚集指数、破碎率、血清黄嘌呤氧化酶活性（XOD）、血浆纤维蛋白原、血液黏度显著升高,红细胞的取向指数、电泳率、血清超氧化物歧化酶活性（SOD）、活化部分凝血酶时间（APTT）和凝血酶原时间（PT）显著降低。结论 无症状高尿酸血症水平下机体氧化应激增强,使大鼠红细胞流变特性的发生不良变化,血液处于高黏高凝状态。研究结果提示临床诊治中应对无症状高尿酸血症正确认识并及时干预。     

无症状高尿酸血症大鼠血液流变学和氧化应激

目的从血液流变学的角度对长期无症状高尿酸血症开展系统研究,为该症的临床处理提供参考依据。方法将20只SD大鼠随机平均分为空白对照组和模型组。通过对大鼠腹腔注射250 mg/(kg·d)氧嗪酸钾诱导8周无症状高尿酸血症模型,采血测量尿酸水平、血液流变学指标、氧化和抗氧化指标。结果模型组大鼠红细胞的聚集指数、破碎率、血清黄嘌呤氧化酶活性(XOD)、血浆纤维蛋白原、血液黏度显著升高,红细胞的取向指数、电泳率、血清超氧化物歧化酶活性(SOD)、活化部分凝血酶时间(APTT)和凝血酶原时间(PT)显著降低。结论无症状高尿酸血症水平下机体氧化应激增强,使大鼠红细胞流变特性发生不良变化,血液处于高黏高凝状态。研究结果提示临床诊治中应对无症状高尿酸血症正确认识并及时干预。     

液相色谱-质谱研究高尿酸血症大鼠血清代谢组学

目的利用液相色谱-串联质谱技术,研究高尿酸血症(HUA)大鼠整体代谢谱的改变,筛选与高尿酸血症相关的潜在生物标志物。方法通过腺嘌呤和氧嗪酸钾灌胃3周,同时自由进食含10%酵母膏饲料方法建立高尿酸血症大鼠模型。采用基于超高效液相色谱-质谱(UPLC-MS/MS)的代谢组学方法,运用主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)分析比较模型组与正常大鼠血清的代谢谱差异。结果与对照组大鼠相比,在高尿酸模型组大鼠中发现并鉴定出14种潜在生物标志物,分别为尿酸、次黄嘌呤、尿囊素、肌酐、马尿酸、犬尿氨酸、色氨酸、硫酸吲哚酚、硫酸对甲酚、牛磺酸、棕榈酸、硬脂酸、溶血磷脂酰胆碱(LPC)(17∶0)和LPC(18∶0)。提示,高尿酸血症影响大鼠嘌呤代谢、氨基酸代谢、胆汁酸代谢、脂肪酸代谢及菌群代谢。结论本研究筛选出高尿酸模型大鼠血清中的14种差异代谢物,有助于解释高尿酸血症引起的代谢改变,可望为高尿酸血症的早期筛查、诊断和治疗提供帮助。     

氯沙坦钾下调尿酸性肾纤维化大鼠肾小管上皮细胞尿酸转运蛋白-1的表达

目的研究氯沙坦钾对高尿酸血症致尿酸性肾纤维化大鼠肾小管上皮细胞尿酸转运蛋白-1(URAT1)表达的影响。方法将大鼠随机分为正常组、模型组(以腺嘌呤100 mg/kg+乙胺丁醇250 mg/kg的混悬液灌胃造模)、氯沙坦钾低、中和高剂量灌胃治疗组[分别为25、50和75 mg/(kg·d)]。各组于造模后第1、2、3和4周检测大鼠血尿酸、血肌酐、尿素氮、尿酸、尿肌酐和尿酸排泄分数,用HE和Masson染色法观察尿酸性肾纤维化大鼠病理变化,Western blot检测肾小管上皮细胞URAT-1蛋白的表达。结果随着时间的延长,模型组大鼠血尿酸水平显著高于正常组(P0.01),尿尿酸水平低于正常组(P0.01);各治疗组血尿酸水平下降,尿尿酸水平升高,以高剂量组为著(P0.05);模型组肾小管间质损伤指数明显高于同期正常组(P0.05),氯沙坦钾干预后肾小管间质损伤指数明显降低(P0.05); URAT1蛋白表达在模型组各时间段升高(P0.05),且随着病理损害的进展呈现上升趋势,经氯沙坦钾干预后表达明显下降(P0.05)。结论氯沙坦钾可下调URAT1高表达,降低高尿酸血症大鼠的血尿酸水平。     

长期单纯高尿酸血症大鼠主动脉病理变化

目的探索长期单纯高尿酸血症(HU)能否造成大鼠主动脉的病理变化。方法将大鼠随机分为对照组和HU模型组,模型组使用2%的氧嗪酸钾饲料和100μmol/L的尿酸水饲养,后期增加氧嗪酸钾灌胃建立长期HU动物模型,使用HE染色观察大鼠主动脉内膜-中膜厚度、内皮炎性细胞浸润以及脂纹、脂斑的形成,使用免疫组化检测大鼠主动脉e NOS、ET-1、ICAM的表达,使用ELISA检测ET-1、ICAM的含量、酶法检测血清NO含量。结果 HU组大鼠可见动脉壁内膜-中膜厚度轻度增加;浸润于内膜的炎性细胞数轻度增多。HU组主动脉内膜e NOS表达较对照组明显减少,ET-1、ICAM表达显著高于对照组(P0.05),HU组大鼠血清ET-1(P0.05)、ICAM(P0.01)均较对照组显著升高,NO(P0.01)较对照组显著降低。结论长期单纯高尿酸血症(12周)可以造成S-D大鼠主动脉早期内皮损伤,但不能形成典型动脉粥样硬化。     

芹菜籽提取物对高尿酸血症模型大鼠的血尿酸以及 抗氧化能力的影响

目的 本实验采用腺嘌呤联合乙胺丁醇诱导大鼠高血尿酸症的造模方法,观察芹菜籽提取物对高尿酸血症大鼠的降血尿酸及抗氧化作用,并进一步观察大鼠肾脏的病变。方法 雄性SD大鼠105只适应性饲养一周,随机分组,每组15只,A组（正常对照组）、B组（模型对照组）、C组（西芹3000组）、D组（别嘌醇组）、E组（低剂量组）、F组（中剂量组）、G组（高剂量组）。模型组及各给药组分别给予腺嘌呤100 mg/（kg·d）+盐酸乙胺丁醇300 mg/（kg·d）于造成高尿酸动物模型,每天于造模后4 h给予治疗药物。C组给予西芹3000片,24 mg/100g体重,每100 g给予0.5 ml体积灌胃;D组给予别嘌醇2.4 mg/100g;D、F、G组分别给予芹菜籽提取物70、140、280 mg/100g（E组灌胃按照560 mg/100g体重灌胃一周后改为70 mg/100g体重芹菜籽提取物溶液）。模型组和对照组分别给予等体积的蒸馏水灌胃。大鼠每周记录体重。实验的第三周结束后,禁食12 h,取腹主脉血,检测肾功能指标、血清SOD、T-AOC活性和MDA水平以及肾脏病理切片。结果 造模过程中大鼠体重明显降低,药物治疗对大鼠体重无明显改善。模型组大鼠肾指数明显增加,药物治疗组队肾脏指数无明显改善,但是芹菜籽提取物中剂量的肾脏指数明显增加。模型组大鼠尿酸明显增加,肾功能明显降低,芹菜籽提取物低剂量和高剂量均能明显降低尿酸水平,提高大鼠肾脏功能。模型组大鼠血清超氧化物歧化酶活性明显降低（P＜0.001）,西芹片和芹菜籽提取物可明显增加SOD活性。模型组大鼠总抗氧化能力明显增加,药物治疗对总抗氧化能力无明显影响。结论 芹菜籽提取物有明显降低尿酸的作用,以高剂量为优,且降尿酸效果和别嘌呤醇相似,优于西芹3000片;芹菜籽提取物对高尿酸大鼠肾功能有明显保护作用;芹菜籽提取物有明显抗氧化作用,表现为降低MDA和增加SOD,对总抗氧化作用不明显。     

α-硫辛酸减轻高尿酸血症大鼠氧化应激损伤

目的观察α-硫辛酸对高尿酸血症大鼠氧化应激和血管内皮细胞形态的影响。方法建立高尿酸血症大鼠模型3周后,每天给予10、30和90 mg/kg不同剂量的α-硫辛酸,灌胃2周,另设对照组,分析大鼠血清尿酸、SOD、GSH-Px、CAT和MDA水平,取胸主动脉,Westernblot法检测SOD和CAT蛋白表达,同时光镜和电镜观察胸主动脉血管内皮形态和超微结构。结果模型组大鼠血清尿酸、SOD、GSH-Px、CAT酶活力均低于对照组,MDA含量高于对照组,胸主动脉SOD及CAT蛋白表达低于对照组(P0.05);α-硫辛酸干预后,大鼠血清尿酸和MDA水平明显降低,中、高剂量组SOD酶活力和胸主动脉SOD及CAT蛋白表达均升高(P0.05);电镜显示高尿酸血症大鼠胸主动脉内皮细胞水肿、脱落,内膜凸起,线粒体增多,经α-硫辛酸干预后,中、高剂量组胸主动脉内皮水肿、凸起数量减少,线粒体数量一过性增加。结论α-硫辛酸可增加高尿酸血症大鼠抗氧化酶活性和蛋白表达,缓解氧化应激,保护血管内皮细胞。     

Impaired feeding responses to intragastric, intraperitoneal, and subcutaneous injections of 2-deoxy-D-glucose in rats with zona incerta lesions

Rats with rostromedial zona incerta lesions displayed severely attenuated feeding responses to intragastric injections of 750, 1000, or 1250 mg/kg of 2-deoxy-D-glucose (2-DG) which elicited optimal feeding and few debilitating side effects in neurologically intact controls. Rats with ZI lesions also ate little, if at all, in response to low doses (200 and 300 mg/kg) of 2-DG administered subcutaneously which were approximately as effective in controls as the intragastric injections of much larger doses. The experimental animals also responded poorly to a standard (600 mg/kg) intraperitoneal (IP) injection of 2-DG but showed only a small impairment in responding to 8 Units/kg of insulin. These results suggest that less stressful routes of administration do not ameliorate the ZI rat's severe deficit in responding to 2-DG that has been reported after IP injections of large doses of the compound, and replicate the observation that insulin feeding is impaired relatively little if at all.     

去卵巢骨质疏松模型大鼠的番茄红素干预

背景：有研究表明番茄红素作为一种抗氧化物质能够减低患慢性疾病的风险。 目的：建立去卵巢骨质疏松大鼠模型,通过给去卵巢大鼠灌服不同剂量的番茄红素,观察其对实验性骨质疏松的保护作用。 方法：切除6月龄SPF级雌性Wistar 未生育大鼠双侧卵巢1周,建立去卵巢骨质疏松大鼠模型,分别给予苯甲酸雌二醇,番茄红素10 mg,20 mg进行干预。 结果与结论：各组给药12周后,番茄红素   高低剂量组与卵巢切除组比较子宫质量,血清中的钙、磷含量,骨小梁面积百分比,骨小梁数目增加,血清中超氧化物歧化酶活性,骨密度和骨生物学性能均明显增高       (P < 0.05);血清中碱性磷酸酶,尿中脱氧吡啶啉,丙二醛,骨小梁分离度和破骨细胞数均减少(P < 0.05)。结果证实,番茄红素能明显缓解去卵巢引起的子宫萎缩,清除体内的自由基,改善去卵巢大鼠的氧化应激状态,减少骨吸收增加骨形成。      

5-HT1A受体激动剂乌拉地尔对小鼠吗啡戒断反应与血浆及脑内NO含量的影响

目的 :观察 5 -HT1A受体激动剂乌拉地尔 (urapidil)对小鼠吗啡戒断反应、血浆及脑内NO含量的影响。方法 :皮下注射定量吗啡 ,建立小鼠吗啡依赖模型。第 6天早 8:0 0用不同剂量的 5 -HT1A受体激动剂乌拉地尔给小鼠腹腔注射 (ip) ,8:2 0纳络酮催瘾 ,观察小鼠戒断时出现跳跃反应次数和体重丢失 ,评定小鼠戒断反应的强度。用硝酸还原法检测血浆和脑内NO的含量。结果 :三种不同剂量 (10 0 ,2 0 0 ,40 0mg kg-1)的乌拉地尔可抑制小鼠吗啡戒断反应 ,并在此剂量范围内呈量效关系。其中 40 0mg kg-1的乌拉地尔可使血中NO升高 ,但使脑内NO含量降低。结论 :5 -HT1A受体激动剂乌拉地尔可抑制小鼠吗啡戒断反应及脑内NO含量的升高     

草药瑞香狼毒丙酮提取物与低剂量卡马西平或丙戊酸镁配伍的抗惊厥研究

目的:探讨草药瑞香狼毒丙酮提取物(AESC)与西药卡马西平(CBZ)、丙戊酸镁(VPM)配伍使用后抗癫痫效果,并与西药单药进行比较。方法:观察AESC和CBZ、VPM不同的配伍方式和剂量,对大鼠癫痫模型、小鼠电休克惊厥模型、小鼠戊四唑惊厥模型和小鼠印防已毒素惊厥模型的作用,并观察AESC对健康自愿受试者CBZ和VPM血药浓度的影响。结果:AESC 500 mg/kg与CBZ 30 mg/kg及VPM 68 mg/kg配伍后对上述三种模型的抗惊厥效应明显优于单用CBZ、VPM组(P<0.01)。结论:采用AESC与小剂量抗惊厥西药CBZ或VPM合理配伍使用可提高抗惊厥效应及减少抗惊厥西药剂量,从而减少西药剂量相关的副作用,具有抗惊厥效应好、抗癎谱广、减少副作用等优点。     

Antihyperlipidemic and antiinflammatory effect of Bhallataka nuts in ameliorating the alterations in lipid metabolism and inflammation in diabetes-induced cardiac damage in rats

Semecarpus anacardium Linn., which belongs to the Anacardiaceae family, has been used in both Ayurveda and Siddha system against various ailments. The present study was carried out to establish the antihyperlipidemic and antiinflammatory effect of S. anacardium Linn. nut milk extract (SA) in diabetes-induced cardiovascular complications in rats. Type 2 diabetes was induced in rats by feeding them with a high-fat diet for 2 weeks followed by intraperitoneal injection of streptozotocin (STZ) 35 mg/kg body wt twice 24 h apart dissolved in olive oil and left for 12 weeks to develop cardiovascular complication. High-fat diet and STZ induction significantly (p?相似文献   

Rat urinary bladder epithelial lesions induced by acrolein

Acrolein, a constituent of cigarette smoke and a metabolite of cyclophosphamide, has been shown to induce acute cytotoxicity of the rat urinary bladder mucosa when instilled directly into the bladder lumen. To evaluate the effects of systemic administration, we examined the rat urinary bladder following intragastric or intraperitoneal administration of acrolein to male F344 rats. In an initial experiment, acrolein was administered at a dose of 25 mg/kg, which proved to be extremely toxic. Five of 12 rats injected intragastrically and 5 of 12 injected intraperitoneally died within 24 hrs. After 2 days, 3 of the 3 surviving rats injected intraperitoneally had focal simple hyperplasia of the urinary bladder. None of the rats injected intragastrically had bladder hyperplasia. In a second experiment, acrolein was administered by intraperitoneal injection at doses of 0.5, 1, 2, 4, and 6 mg/kg. Five days later, the labeling index of the bladder mucosa was evaluated by autoradiography. In rats injected with 6 mg/kg of acrolein, the labeling index was significantly increased compared to the other doses and compared to a vehicle injection control group. These data indicate that sufficient acrolein reaches the urinary bladder to induce a proliferative response following intraperitoneal administration.     

Nephroprotective effect of Semecarpus anacardium on diabetic nephropathy in type 2 diabetic rats

Semecarpus anacardium Linn. (Anacardiaceae), commonly known as marking nut is found in sub-Himalayan regions and also in central parts of India. This study is aimed at evaluating the protective effect of the drug S. anacardium nut milk extract (SA) on diabetes-induced damage in kidney of type 2 diabetic rats. Diabetic nephropathy was induced in rats by feeding them with a high fat diet for 5 weeks followed by i.p. injection of 35 mg/kg body weight (b.wt.) and left for 8 weeks. Diabetic nephropathy-induced animals were treated with SA at a dosage of 300 mg/kg b.wt. dissolved in olive oil for 8 weeks. Treatment with the drug SA decreased the levels of urea, uric acid and creatinine. The drug SA significantly decreased the levels of marker enzymes and lipid peroxides while increasing the levels of antioxidant enzymes. The histopathological alterations in kidney tissues were also found to be normalized after treatment with SA nut milk extract. No significant alterations were observed in drug alone-treated group of rats. The present study suggests that SA demonstrated antioxidant activity in diabetic nephropathy rats. The potential nephroprotective effect is plausibly due to its underlying antioxidant role.     

The effect of cherry sticks extract on the levels of glycoproteins in alloxan-induced experimental diabetic mice

This study was designed to evaluate the effect of ethanolic cherry sticks extract on the levels of glycoproteins in alloxan-induced diabetic mice. Forty-five adult male albino mice were divided equally into three groups: Group 1: control, Group 2: diabetic mice, Group 3: diabetic mice treated with cherry sticks extract as well as to eighteen mice treated with cherry sticks extract only for toxicity test. All treatments were administered via an intragastric tube. Diabetes was induced in the mice of Group 3 by an intraperitoneal injection with 100 mg/kg body weight of alloxan. Oral administration of cherry sticks extract at a concentration of 250 mg/kg body weight for 15 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as those of hexose, hexosamine, fucose, and sialic acid in the diabetic mice treated with the cherry sticks extract as compared to untreated diabetic mice, with no adverse effects in mice treated only with cherry sticks extract. In conclusion, cherry sticks extract proved to have a beneficial effect on the diabetic mice in this study. In light of these advantageous results, it is advisable to broaden the scale of use of cherry sticks extract in a trial to alleviate the adverse effects of diabetes.     

黄芪多糖联合顺铂对小鼠Lewis肺癌移植瘤Caspase-3、Smac/Diablo表达的影响

目的观察黄芪多糖(APS)及联合顺铂(DDP)对小鼠Lewis肺癌(LLC)移植瘤凋亡蛋白Caspase-3、Smac/Diablo表达的影响,探讨黄芪多糖抗肿瘤的机制。方法 90只C57BL/6 J小鼠,随机分为9组,正常组、模型组、APS低、中、高剂量组、DDP组、联合低、中、高剂量组,每组10只。除正常组外,其余80只均接种肺癌移植瘤细胞(1×1010/L)于右前肢腋窝皮下,制造模型为荷瘤小鼠。制造模型次日起,治疗组的小鼠给予腹腔注射0.3 ml药物。顺铂每周注射1次,其余药物每日1次,正常组和模型组注射等体积生理盐水,连续20 d,于第21天处死。肿瘤组织进行HE染色并行病理学观察;免疫组织化学染色和图像分析方法检测移植瘤细胞中的Caspase-3及Smac/Diablo的表达。结果荷瘤小鼠在APS(高)、联合(中)、联合(高)组的体质量变化,具有统计学意义。与模型组小鼠比较,肿瘤组织的病理组织学HE显示,APS(高)联合顺铂组的肿瘤细胞坏死最为明显;免疫组织化学法表明,治疗组的肿瘤组织中Caspase-3、Smac/Diablo蛋白表达水平均升高,联合(高)组升高最明显。结论 APS及联合化疗药物DDP能抑制小鼠Lewis肺癌细胞的生长,其机制可能与升高Caspase-3、Smac/Diablo的表达有关。