肾提取液对大鼠庆大霉素肾毒性的防治作用研究

研究乳猪肾提取液对大鼠庆大霉素肾毒性的防治作用。新鲜乳猪肾经匀浆、超滤等处理得肾提取液。肌注庆大霉素100mg／（kg·d）×7d制成大鼠急性肾衰模型。制模同时及造模后分别ip肾提取液15mg／（kg·d）,观察大鼠血清尿素氮（Bloodureanitrogen,BUN）、肌酐（Cr）及肾组织变化情况。实验结束时,预防组BUN为9．30±2．60mmol/L,Cr为125．00±26．60μmol／L;模型组BUN为12.80±2.45mmol／L,Cr为167．00±39．60μmol／L,P＜0．01。结果表明,肾提取液可明显减轻庆大霉素对大鼠的肾损害。     

关木通与川木通的性状区别及意义

关木通与川木通均以木通入药，外形雷同，功效、性能、性味、主治相似，都己载人《中国药典》。历代医家视关木通为上品，价格高于川木通，但近来发现关木通具肾毒性，建议不用。故正确地鉴别它们，实属重要。     

姜黄素对大鼠环孢素肾毒性的防治作用

目的:观察姜黄素对环孢素肾毒性的防治作用。方法:以30 mg·kg~(-1)·d~(-1)的环孢素灌胃28 d,以姜黄素治疗和预防环孢素所致大鼠肾毒性损伤,观察体重,尿量,血尿素氮和血肌酐的变化,光镜观察肾脏病变以及测定肾脏血红素加氧酶(HO- 1)和碱性成纤维细胞因子(bFGF)的mRNA和蛋白质的表达含量。结果:与正常组相比,使用环孢素的大鼠体重降低(P<0.05),尿量,血尿素氮,肌酐均上升(P<0.05);肾脏损伤性病变较典型;HO-1表达少而bFGF表达多(P<0.01)。姜黄素治疗后使其肾毒性大鼠的体重回升(P<0.05),尿量,血尿素氮和肌酐均回降(P<0.05);病理改变显著好转;HO-1表达回升而bFGF回降(P<0.01);且预防组疗效优于治疗组。结论:姜黄素可防治CsA环孢素所导致的肾毒性损伤,预防效果优于治疗效果。其机制与HO-1和bFGF的表达有关。     

肾茶胶囊对大鼠脏器长期毒性的实验研究

目的考察肾茶胶囊对大鼠脏器的长期毒性反应及毒性程度,研究毒性靶器官及其损伤的可逆性。方法大鼠灌胃给予肾茶胶囊1.62、4.86、14.58g/kg(约相当于人拟临床等效剂量的10、30、90倍),设空白对照组,1次/d,连续灌胃给药24周后各剂量组随机处死,系统尸解,检查脏器系数。结果 12周及24周高剂量组、中剂量组、低剂量组试验大鼠脏器系数指标与对照组相比,组间未见显著差异和异常改变,也未见毒理学意义变化和延迟性毒性反应。结论肾茶胶囊对脏器的长期毒性较低,未发现毒性靶器官,可安全地应用于临床。     

益母草醇提取物对大鼠肾毒性损伤作用研究

目的观察长期、大量给予益母草醇提取物致大鼠肾毒性损伤的作用和程度。方法按90天毒性实验法,除观察一般状况外,监测大鼠尿常规、尿微量蛋白及肾毒性相关指标,并进行肾组织病理学检查。结果益母草醇提取物可导致血中尿素氮（BUN）、肌酐（Cr）含量增高,肾脏重量和肾／体比值增大,病理组织学检查可见不同程度的肾小管损伤,上述变化随剂量的增加而逐渐加重。结论益母草醇提取物长期给药后可导致大鼠明显的肾毒性损伤。     

姜黄素对大鼠环孢素慢性肾毒性防治作用研究

目的 观察姜黄素对环孢素(CSA)肾毒性的防治作用。方法 将30只大鼠随机分为4组，即正常组6只，模型组、治疗组和预防组各8只。正常组给予橄榄油30 mg·kg-1·d-1灌胃4周；模型组以CSA30 mg·kg-1·d-1灌胃4周；治疗组以CSA30 mg·kg-1·d-1灌胃2周后,再给予姜黄素200 mg·kg-1·d-1灌胃2周；预防组给予CSA30 mg·kg-1·d-1与姜黄素200 mg·kg-1·d-1联合灌胃4周。观察给药前后各组大鼠的体重变化，以及给药后24 h尿量、血肌酐、尿素氮和肾脏病理变化。用免疫组织化学和RT-PCR法检测各组大鼠肾组织HO-1和bFGF表达情况。结果 与正常组相比，模型组大鼠给予CSA后体重下降（P＜0.05＝，尿量增多（P＜0.05＝，尿素氮、肌酐上升（均P＜0.05＝，肾脏组织出现较典型的病理变化，HO 1表达显著下降（P＜0.01＝，bFGF表达增加（P＜0.01＝。与模型组相比，治疗组和预防组HO-1表达增加（均P＜0.01＝，bFGF表达下降（均P＜0.01＝。结论姜 黄素可改善CSA所导致的肾毒性，可能是通过增加HO-1、降低bFGF的表达发挥抗CSA肾毒性的作用。     

环孢素A大鼠慢性肾毒性模型的建立

目的建立大鼠环孢素A(CsA)慢性肾毒性模型. 方法 SD大鼠随机分为对照组和CsA(25 mg/(kg·d))组,每组6只,用药4周后观察其尿量、肾功能和肾组织形态学的改变.结果与对照组相比,CsA组大鼠血肌酐升高,病理上表现为不同程度肾小管上皮细胞浊肿、空泡变性、肾间质纤维化、钙化.结论 CsA25 mg/(kg·d)用药4周后可建立大鼠慢性肾毒性模型.     

HPLC测定川木通中齐墩果酸的含量

目的建立测定水解后的川木通药材中齐墩果酸含量的方法。方法采用HPLC法。Alltima C18色谱柱(250 mm×4.6 mm,5μm);流动相为甲醇-水-冰醋酸-三乙胺(89∶11∶0.04∶0.02);检测波长207 nm;流速1.0 ml.min-1;柱温45℃。结果齐墩果酸色谱峰分离度良好,线性范围为0.1003~8.024μg(r=0.9999,n=5),方法的检测限和定量限分别为0.3μg.ml-1和1.0μg.ml-1。平均回收率为96.1%,RSD=2.8%(n=5)。结论所用结果准确,重复性好,专属性强,可为川木通药材质量控制提供科学的依据。     

中药配伍对关木通中马兜铃酸A含量的影响

目的：运用高效液相色谱法找出同关木通配伍后，使其中马兜铃酸A含量显著降低的中药及其最佳配比。方法：关木通与筛选药物配伍后，用反相高效液相色谱法（RP-HPLC）测定马兜铃酸A吸收值判断其含量是否降低。结果：当归、丹皮、生地、熟地、大黄可显著降低关木通中马兜铃酸A的含量。其中，当归与关木通质量比为1：1，生地与关木通质量比为0．5：1，丹皮与关木通质量比为1：1是最佳配比。结论：关木通配伍上述中药后，马兜铃酸A的含量能显著降低。     

东北地区铁线透骨草药材的HPLC指纹图谱研究

目的:建立铁线透骨草药材的高效液相色谱(HPLC)指纹图谱。方法:采用HPLC法。色谱柱为Hedera ODS-2 C18,流动相为乙腈-0.5%磷酸溶液(梯度洗脱),流速为1.0 m L/min,检测波长为338 nm,柱温为30℃,进样量为20μL。以芦丁为参照物,测定10批铁线透骨草药材的HPLC图谱,采用《中药色谱指纹图谱相似度评价系统》(2004A版)进行共有峰确定和相似度评价。结果:10批铁线透骨草药材有16个共有峰,相似度均>0.9。经验证,10批药材样品HPLC图谱与对照指纹图谱具有较好的一致性。结论:所建指纹图谱可为东北地区铁线透骨草药材的鉴别和质量评价提供参考。     

Circadian variations in the renal toxicity of gentamicin in rats

The hypothesis that sublethal doses of aminoglycosides cause renal tubule disorders resulting in changes of urine enzyme levels was investigated. The renal status following injection of a single sublethal dose of gentamicin (200 mg/kg) at different times during a 24 h cycle was studied. Increased excretion of gamma-glutamyl transferase, alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, used clinically as markers for tubule toxicity of aminoglycosides, was maximal when gentamicin was administered to rats at 2 p.m. and was minimal when injected at 8 p.m. These significant differences in enzyme excretion as a function of injection time are correlated with the concentration of gentamicin in the urine and in the renal cortex.     

Critical concentration of cadmium for renal toxicity in rats

To evaluate a critical concentration concept of cadmium (Cd) toxicity on the kidney, relationships of renal Cd level with urinary excretion of various substances--i.e., metallothionein, alkaline phosphatase, lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, total protein, Cd, copper, and zinc--were studied in Cd-injected rats. At the renal Cd concentration of 100-200 micrograms/g tissue, a dramatic increase of all these substances in urine was observed, supporting the idea of the critical concentration proposed by Friberg and co-workers (1974). The significance of increase of urinary metallothionein below this level is also discussed.     

Effect of N-benzyl-d-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 mumol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 mumol Cd as Cd-MT/kg) and thereafter they received three injections of BGD (400 mumol/kg) daily for 3 days. Urinary protein concentration and aspartate aminotransferase (AST) activity significantly increased 1 day after Cd-MT treatment and decreased to control levels at 9 days after the treatment. Urinary excretion of glucose and amino acids rose gradually reaching maximum levels 5 days after Cd-MT treatment and returned to the control levels at 9 days. BGD injection significantly reduced the increases in the urinary excretion of protein, AST, glucose and amino acid, which were produced by Cd-MT treatment. Significant increases in urine volume were observed after Cd-MT treatment. BGD injection inhibited the increase in urine volume caused by Cd-MT treatment. A long time interval (12 and 24 h) between the administrations of Cd-MT and BGD resulted in a decreased protective effect of BGD against Cd-MT-induced renal damage. Following Cd-MT injection, the major route of excretion of cadmium (Cd) was via the urine and the kidney was the major site of accumulation of Cd. BGD injection remarkably increased the urinary excretion of Cd, resulting in a significant reduction in the kidney Cd concentration. The results of this study indicate that BGD injection is effective in decreasing the Cd concentration in the kidney, resulting in the protective effect on Cd-MT-induced renal damage.     

Chronic hepatic and renal toxicity by cadmium in rats

Recently there has been an increased interest in the toxic effects from long term exposure of low levels of cadmium (Cd) in diet. Male, Sprague-Dawley rats were treated with 0, 25, 50, 75 ppm Cd mixed in diet continuously for 180 days. A significant decrease in body weight gain was observed in all Cd treated animals. Serum glucose, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvic transaminase (SGPT) were increased parallel to Cd concentration and treatment time. Measured hepatic and renal gluconeogenic enzymes, viz. glucose-6-phosphatase, fructose-1, 6-bisphosphatase and phosphoenolpyruvate carboxykinase were increased with higher Cd dose and time. Low concentration of Cd (25 ppm) had minimal effect with shorter treatment length. Fructose-1, 6-bisphosphatase was found to be very sensitive for assessing Cd-induced nephrotoxicity. Increased serum glucose level and gluconeogenic enzyme activities suggest that Cd might interfere in protein metabolism.     

Ethylene glycol induced renal toxicity in female Wistar rats

The calcium oxalate nephrolithiasis due to ethylene glycol treatment has long been observed in male species but the prevalence of calcium oxalate nephrolithiasis in female species due to ethylene glycol has been still a subject of controversy. Ethylene glycol was administered in drinking water at three different doses (0.4%, 0.75% and 1.0%, v/v) for 28 days in female Wistar rats. Ethylene glycol treatment caused significant decrease in body weight and corresponding increase in relative organ weight with significant hypercalciuria, hyperoxaluria and proteinuria as well as increased retention of calcium, oxalate, phosphate and total protein in kidney in a dose — and time — dependent manner. However, calcium level was significantly reduced in the serum while an increase in total protein and phosphate level in serum was observed. Furthermore, there was a significant reduction in magnesium level in urine, serum and kidney due to ethylene glycol. The effects were also confirmed in histopathological studies.     

Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats

1. The present study investigated the possible protective effects of thymoquinone (TQ), a compound derived from Nigella sativa with strong anti-oxidant properties, against gentamicin (GM)-induced nephrotoxicity. 2. A total of 40 adult male Wistar albino rats was divided into four groups. Rats in the first group were injected daily with normal saline (2.5 mL/kg, i.p.) for 8 consecutive days, whereas rats in the second group received TQ (50 mg/L in drinking water) for 8 consecutive days. Animals in the third group were injected daily with GM (80 mg/kg, i.p.) for 8 consecutive days, whereas animals in the fourth group received a combination of GM (80 mg/kg, i.p.) and TQ (50 mg/L in drinking water) for 8 consecutive days. 3. Gentamicin resulted in a significant increase in serum creatinine, blood urea nitrogen (BUN), thiobarbituric acid-reactive substances (TBARS) and total nitrate/nitrite (NOx) and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) and ATP levels in kidney tissues. 4. Interestingly, TQ supplementation resulted in a complete reversal of the GM-induced increase in BUN, creatinine, TBARS and NOx and decrease in GSH, GPx, CAT and ATP to control values. Moreover, histopathological examination of kidney tissues confirmed the biochemical data, wherein TQ supplementation prevents GM-induced degenerative changes in kidney tissues. 5. Data from the present study suggest that TQ supplementation prevents the development of GM-induced acute renal failure by a mechanism related, at least in part, to its ability to decrease oxidative stress and to preserve the activity of the anti-oxidant enzymes, as well as it ability to prevent the energy decline in kidney tissues.     

二硫化碳的大鼠肾脏毒性

ＣＳ２亚急性动物染毒实验结果发现：各染毒组大鼠尿ＡＫＰ活性均较对照组增高（Ｐ＜０．０１或Ｐ＜０．０５）；１２５０ｍｇ／ｍ３染毒组大鼠红细胞ＬＰＯ较对照组升高（Ｐ＜０．０１）；红细胞和肾组织匀浆ＳＯＤ活性随染毒剂量增高呈先上升后下降的变化；１２５０ｍｇ／ｍ３染毒组大鼠肾组织近曲小管上皮细胞浊肿，线粒体肿胀变性。提示ＣＳ２所致肾损害似与组织细胞自由基引发脂质过氧化有关。