益肾降浊胶囊治疗慢性肾功能衰竭的实验研究

目的探讨益肾降浊胶囊对慢性肾功能衰竭(简称慢性肾衰)大鼠的治疗作用。方法采用阳离子化牛血清白蛋白造成大鼠膜性肾病诱发慢性肾衰后,造模后的大鼠随机分为5组,即空白对照组、模型组、阳性药物肾衰宁组、益肾降浊胶囊高、中、低剂量组。每天定时定量灌胃给予药物,空白对照组组和模型组灌胃给予等量生理盐水。给药治疗6周后,观察各组大鼠的一般状态,测定各组大鼠24h尿蛋白量,测定大鼠血清中肌酐(Scr)及尿素氮(BUN)含量;观察肾脏组织病理变化的情况,检测超氧化物歧化酶(SOD)的活性和丙二醛(MDA)含量。结果与模型组比较,通过益肾降浊胶囊治疗能够有效改善慢性肾衰大鼠的一般生存状态,显著降低大鼠24h尿蛋白量、血清肌酐(Scr)、尿素氮(BUN)的含量。病理结果显示,益肾降浊胶囊可缓解慢性肾衰大鼠的肾小球硬化及炎性细胞浸润。益肾降浊胶囊能够有效的增加CRF大鼠的肾脏组织SOD活性并降低MDA含量。结论益肾降浊胶囊能够有效的治疗大鼠慢性肾功能衰竭。     

绿茶改善慢性肾衰竭大鼠肾功能的实验研究

采用“单肾切除加腺嘌呤灌胃法”建立大鼠慢性肾衰竭模型。治疗组用绿茶液灌胃,对照组用尿毒清溶液灌胃。每周测24h尿蛋白定量1次,给药4周后处死大鼠,取血测血清肌酐（SCr）、尿素氮（BUN）、血钙、血磷、红细胞计数、血红蛋白含量。实验结果表明,绿茶能够显著改善大鼠整体状况、降低24h尿蛋白量、改善肾功能、缓解肾性贫血,说明绿茶对单侧肾切除后腺嘌呤性慢性衰竭大鼠的肾功能具有一定的改善作用。     

绿茶抗大鼠肾间质纤维化作用的实验研究

采用"单肾切除加腺嘌呤灌胃法"建立大鼠慢性肾衰竭模型。治疗组予绿茶液灌胃治疗,对照组予尿毒清溶液灌胃治疗,连续治疗28天。取大鼠肾脏石蜡切片分别进行HE染色、PASM染色、Masson染色、Sirius Red染色、Mallory染色,光镜下观察大鼠肾组织5种染色的病理形态学改变,PASM染色、Masson染色、Sirius Red染色随机选择进行肾脏组织病理学图像分析。绿茶组在肾间质纤维化面积、肾小球系膜积分光密度值、肾间质中I、Ⅲ型胶原分布面积等方面的作用与模型组对比,P<0.05。说明绿茶能够减轻腺嘌呤对大鼠肾间质的病理损害,绿茶有抗肾间质纤维化的作用,并且能抑制I、Ⅲ型胶原纤维的增生,这可能是绿茶防治肾间质纤维化、延缓慢性肾衰竭发展进程的机制之一。     

参泽舒肝胶囊及其拆方连续多次给药对大鼠肾功能及肾组织形态的影响

目的 通过大鼠连续给药26周肾功能及肾组织形态的观察,明确参泽舒肝胶囊(QF)及其所含成分大黄(DH)、泽泻(ZX)、决明子(JMZ)对肾脏的影响。方法 正常健康大鼠分别灌胃给予QF、DH、ZX、JMZ提取物26周,期间对大鼠的体表特征、体重、饮食、饮水量进行观察,并对尿微量蛋白、CRE、BUN、GSH-PX、SOD含量或酶活性等进行检测,并观察肾脏组织病理形态学变化及肾组织中HIF1β的表达。结果 给药26周末,各给药组对大鼠外观状态、体重、饮食饮水、尿常规均无明显影响。尿微量蛋白、血清CRE、BUN、GSH-PX、SOD含量或酶活性测定值均稳定在一定区间范围内,病理结果显示,对照组、全方高(QFG)、低剂量(QFD)组均可见个别动物肾小管发生轻微肿胀,与对照组比较GF组未见明显形态差异;单独大黄、泽泻、决明子提取物各剂量组不同程度的增加肾小管变性程度的等级,增加发生肾小管变性数量。结论 单独DH、ZX、JMZ长期大量服用会出现一定的肾毒性反应,QF长期给药均未显示明显的肾毒性反应,提示组方以后具有明显的配伍减毒作用,该制剂长期服用安全可靠。     

大豆异黄酮抗高尿酸血症活性研究初探

为研制新型无副作用的降血尿酸药物,在氧嗪酸钾盐诱导小鼠产生高尿酸血症模型的基础上,探讨大豆异黄酮的抗高尿酸活性.将昆明雄性小鼠随机分为6组,即正常对照组、高尿酸血症模型对照组、模型给药组(分为大豆异黄酮25,50和100 mg·kg-1剂量组、别嘌醇5 mg·kg-1剂量组).连续7d每天灌胃氧嗪酸钾盐(250 mg·kg“)1h后灌胃给药.分别测定血清尿酸、肌酐与尿素氮水平及尿液尿酸和肌酐水平.结果表明:与高尿酸血症模型组相比,大豆异黄酮显著或极显著降低高尿酸血症小鼠血清尿酸、肌酐和尿素氮水平,提高24 h尿液尿酸和肌酐排泄量以及尿酸排泄分数.综合考虑,大豆异黄酮通过促进肾脏尿酸排泄作用,从而体现抗高尿酸活性.     

组方优化的阳和胶囊对碘乙酸钠诱导大鼠骨关节炎的作用研究

目的探讨组方优化的阳和胶囊对碘乙酸钠诱导的大鼠骨关节炎的治疗作用及其机制研究。方法采用大鼠膝关节腔内注射4%碘乙酸钠溶液0.1 ml,连续注射7天,建立大鼠骨关节炎模型。于造模后分别灌胃给予组方优化的阳和胶囊高、中、低剂量及阳性对照双醋瑞因胶囊(8.0mg/kg),每日1次,连续给药4周。实验期间每周测定大鼠膝关节肿胀度。实验结束后测定大鼠膝关节灌洗液中NO、PGE-2含量,血清中IL-1β、TNF-α含量,及软骨组织中MMP-1、MMP-13含量。结果实验期间模型组大鼠膝关节显著肿胀(P0.01),各给药组与模型组相比均有不同程度缓解。组方优化的阳和胶囊高、中剂量组能够显著降低膝关节灌洗液中NO、PGE-2含量(P0.01)、显著降低血清中IL-1β、TNF-α含量(P0.01)明显降低软骨组织中MMP-1、MMP-13含量(P0.05)。结论组方优化的阳和胶囊对碘乙酸钠诱导的大鼠骨关节炎具有治疗作用,其机制可能与降低膝关节灌洗液及血清中NO、PGE-2、IL-1β、TNF-α水平及软骨组织中MMP-1、MMP-13含量有关。     

山灵参胶囊对大鼠实验性高脂血症的保护作用

目的观察山灵参胶囊对大鼠实验性高脂血症的保护作用。方法雄性Wistar大鼠60只,取10只作为正常组,其余大鼠喂养高脂饲料6周建立实验性高脂血症模型。造模组按体重随机分为模型组,山灵参胶囊250、500、1000 mg/kg组和阳性药辛伐他汀片30 mg/kg组,各组分别灌胃给药,正常组及模型组给予同体积0.5%的羧甲基纤维素钠。给药30天后,各组大鼠水合氯醛麻醉,腹主动脉取血,检测血清TC、TG、LDL-c、HDL-c、FFA、MDA含量及SOD活性;取肝脏制备匀浆,检测肝组织TC、TG、MDA含量及SOD活性。结果与正常组比较,模型组大鼠血清中TC、TG、LDL-c、FFA及MDA含量均明显升高,肝组织TC、TG及MDA含量亦明显升高,SOD活性降低(P0.05或P0.01)。与模型组比较,山灵参胶囊500、1000 mg/kg剂量组能明显降低大鼠血清TC、TG、LDL-c、FFA及MDA含量,升高SOD活性,并能明显降低大鼠肝组织TC、TG及MDA含量,升高SOD活性(P0.05或P0.01)。结论山灵参胶囊对大鼠实验性高脂血症具有明显保护作用,可能通过减轻肝细胞脂质过氧化损伤,增强机体清除氧自由基能力实现的。     

L-茶氨酸改善慢性应激大鼠抑郁行为作用研究

研究L-茶氨酸对慢性不可预见性温和应激模型大鼠的抗抑郁作用及其机制。建立慢性不可预见性温和应激（CUMS）抑郁大鼠模型,通过糖水偏好实验,旷场实验,明暗箱实验评估L-茶氨酸的抗抑郁作用效果;为了阐释其相关机理,本研究通过酶联免疫法测定了各组大鼠海马和皮层组织中5-羟色胺（5-HT）、去甲肾上腺素（NA）、促肾上腺皮质激素（ACTH）和皮质酮（CORT）的含量,同时也检测了大鼠血清和海马组织中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。结果表明,与空白对照组相比,模型组大鼠糖水偏好度、横穿格数和直立次数、进入明箱中的大鼠数量以及停留的时间极显著降低,显示大鼠抑郁模型构建成功;而与模型组相比,灌胃低高两个剂量L-茶氨酸的大鼠抑郁症状有不同程度改善,尤其高剂量都达到显著水平。同时,L-茶氨酸能显著提升大鼠海马和皮层中5-HT、NA的含量,降低ACTH,CORT的含量,上调大鼠血清和皮层中SOD和GSH-Px的活性,进一步表明了其抗抑郁的功效,其机制可能主要与促进单胺类递质分泌有关。     

人参及灵芝超微粉对酒精所致大鼠慢性肝损伤的保护作用

目的观察人参及灵芝超微粉对酒精所致大鼠慢性肝损伤的保护作用。方法将80只Wistar大鼠随机分为正常组,模型组,人参超微粉低、高剂量(0.25、0.5g/kg)组,灵芝超微粉低、高剂量(0.25、0.5g/kg)组及人参超微粉联合灵芝超微粉低、高剂量(0.25+0.25、0.5+0.5g/kg)组,每组10只。除正常组给蒸馏水外,其余各组均以56%白酒灌胃,第1周为8 mL/kg,以后每周增加1 mL,连续灌胃8周,建立大鼠慢性酒精性肝损伤模型,造模同时灌胃给予人参及灵芝超微粉,观察慢性酒精性肝损伤大鼠肝脏指数、肝功能、脂质过氧化物及细胞炎性因子变化。结果与正常组比较,模型组大鼠体质量明显降低,肝脏指数增加,血清ALT、AST活性及TNF-α、IL-6含量均明显升高,肝组织MDA及TG含量明显升高,GSH含量及SOD活性明显降低(P0.05或P0.01)。与模型组比较,人参、芝超微粉高剂量组及人参联合灵芝超微粉低、高剂量组均能明显增加大鼠体质量,降低肝脏指数,降低血清TNF-α、IL-6含量及AST、ALT活性,并能明显降低肝组织MDA及TG含量,升高GSH含量及SOD活性(P0.05或P0.01)。结论人参及灵芝超微粉对大鼠酒精慢性肝损伤具有明显保护作用,二者联合应用具有协同作用。     

茯砖茶减肥作用研究

探讨了茯砖茶和绿茶对营养型肥胖大鼠的减肥作用。茶叶水提物的低、中、高灌胃剂量分别为：75、150、300mg/kg。结果表明：与肥胖模型组相比,茯砖茶和绿茶均能显著抑制大鼠体质量增长,降低食物利用率、脂肪系数以及Lee氏指数。脂肪细胞观察表明,喂饲茯砖茶和绿茶组大鼠的脂肪细胞中脂滴含量明显减少,脂肪细胞直径明显变小。茯砖茶降低血清甘油三酯的效果优于绿茶。     

The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.     

普洱茶茶褐素对大鼠尿液影响的代谢组学研究

本研究采用核磁共振(NMR)代谢组学法研究普洱茶茶褐素(TB,分子量50 k Da)对大鼠尿液代谢的影响。将实验大鼠分为正常对照组、正常+TB组、高脂组和高脂+TB组,以生物核磁共振技术结合正交偏最小二乘-判别分析(OPLS-DA)研究灌胃高剂量普洱茶茶褐素后大鼠尿液内源性代谢物的变化。结果表明,正常+TB组与正常对照组,高脂+TB组与高脂组的尿液代谢谱有明显差异;筛选出缬氨酸、柠檬酸、牛磺酸、丙酸盐、α-酮戊二酸、β-羟基丁酸等6种普洱茶茶褐素标志性代谢物;普洱茶茶褐素对大鼠尿液的影响可能涉及到氨基酸代谢、能量代谢、三羧酸循环、脂类代谢和氧化应激反应。     

A chronic oral toxicity study of marine collagen peptides preparation from chum salmon (Oncorhynchus keta) skin using Sprague-Dawley rat

Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet.     

Chronic Nicotine Toxicity is Prevented by Aqueous Garlic Extract

Based on the potent antioxidant effects of garlic, we investigated the putative protective role of aqueous garlic extract (AGE) against nicotine-induced oxidative organ damage. Male Wistar albino rats (200–250 g) were injected with nicotine hydrogen bitartrate (0.6 mg/kg; i.p.) alone or with aqueous garlic extract (125 mg/kg; i.p.) for 21 days. At the end of the experimental period (22^nd day) rats were killed by decapitation. The aorta, heart, kidney and urinary bladder tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Blood urea nitrogen (BUN) and creatinine concentrations and lactate dehydrogenase (LDH) levels in blood were measured for the evaluation of renal functions and tissue damage, respectively. Tissues were also examined microscopically.The decrease in GSH levels and increases in MDA level, MPO activity and collagen contents induced by chronic nicotine administration indicated that tissue injury involves free radical formation. Treatment of rats with AGE restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the tissues by chronic nicotine were reversed back to the control levels with AGE. Since AGE administration reversed these oxidant responses, improved renal function and histological damage, it seems likely that AGE protects the tissues against nicotine-induced oxidative damage.     

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.     

Effects of amylose and wheat bran on the levels of blood serum urea nitrogen (BUN), other blood parameters,growth and fecal characteristics in rats

A basal diet (containing 20% soybean protein isolate) was supplemented with limiting amino acids (AA, methionine, threonine and tryptophan); wheat bran (WB, 24.3%); amylose (AM, 10%) or a combination of AA and WB or AM to investigate their effects on the levels of blood serum urea nitrogen (BUN), other blood parameters, growth and fecal characteristics in young rats. After 3 weeks feeding, supplementation of the basal diet with AA or WB resulted in improved growth (gain/food ratio) while the addition of AM had no effect on rat growth. Addition of WB to the basal diet had no effect on BUN while the addition of AA and AM caused about 20 and 12% reduction in BUN values, respectively. Rats fed the AA-AM diet had the lowest BUN values (42% lower than those fed the basal diet). Fresh volume, fresh weight, moisture and dry weight of feces in rats fed the WB diets were about four to five fold higher than in those fed the AM diets. The results suggested that BUN may not be a good predictor of growth and protein quality in diets containing AM or a source of dietary fiber (WB).     

表没食子儿茶素没食子酸酯和维生素C联用对高尿酸血症小鼠血尿酸水平的影响

以KM雄性小鼠为研究对象,酵母膏（7.5 g·kg^-1）和氧嗪酸钾（250 mg·kg^-1）联合给药建立高尿酸血症小鼠模型,探究表没食子儿茶素没食子酸酯（EGCG）和维生素C（Vc）联用对高尿酸血症小鼠血尿酸水平的影响。将小鼠随机分为6组（n=6）：空白组、模型组、别嘌呤醇组（阳性药组）、EGCG组、EGCG联合Vc组和Vc组,连续给药7 d后测定生化指标。结果表明,与模型组相比,EGCG联合Vc组小鼠的血尿酸值（UA）,血尿素氮（BUN）和肌酐（Cr）水平均明显降低（P<0.001）;EGCG与Vc联用明显抑制了肝脏中腺苷脱氨酶（ADA）和黄嘌呤氧化酶（XOD）的活性（P<0.05或P<0.01）,并显著下调了肾脏中葡萄糖转运蛋白9（GLUT9）mRNA的表达（P<0.001）;肾脏切片显示EGCG和Vc联用显著改善高尿酸血症小鼠的肾脏损伤。此外,EGCG与Vc联用对高尿酸血症小鼠的作用效果优于EGCG。     

Effects of taurine on glutathione peroxidase, glutathione reductase and reduced glutathione levels in rats

The aim of the present study is to investigate the effects of oral administration of taurine on endogenous glutathione peroxidase (GPx) and Glutathione Reductase (GR) activities and reduced glutathione (GSH) level in normal rats. Normal saline (Group I) or 5% taurine in normal saline was administered in dose of 50 mg (Group II), 250 mg (Group III) or 500 mg kg(-1) of body weight (Group IV) through intragastric intubation for 60 days. GPx and GR enzyme activities and GSH and taurine levels were determined in liver, heart, stomach, kidney and plasma of normal Wistar rats. GPx activity showed an increase in liver, heart, stomach and plasma. GR activity increased in kidney and decreased in liver and plasma. GSH levels increased in liver, stomach and decreased in kidney. Liver showed an increase and heart, stomach and kidney a decrease in taurine level in taurine administered rats when compared to control rats. The results varied from organ to organ and the observed variations among organs might be related to their respective enzymatic, non-enzymatic antioxidant potential and its functions. From the present study it may be concluded that long term oral administration of taurine affects GPx, GR and GSH levels in normal rats.