Adverse effects in kidney function,antioxidant systems and histopathology in rats receiving monosodium glutamate diet

We investigated the effects of adding of monosodium glutamate (MSG) to a standard diet on oxidative stress in kidney, nitric oxide excretion, renal ions handling and blood pressure. We examined the association of these changes with the effects on renal histology. The study was performed on male Wistar rats (5 weeks old) divided into 3 groups: 1) MSG group were fed a diet supplemented with 3 g of MSG/kg b.w./day, five days a week, and spontaneous ingestion of a 1% MSG solution during 16 weeks; 2) NaCl group were fed a diet with NaCl (1 g/kg b.w./day) and 0.35% NaCl solution permanently alone at the same frequency and time; 3) control group were fed the normal chow and tap water. Sodium, potassium, calcium, phosphorus, creatinine, protein and nitric oxide excretion were analyzed in urine. We utilized clearance techniques to examine glomerular filtration rate and cortical renal plasma flow. We determined the oxidative state and the histopathological changes of renal tissue.Following MSG treatment, absolute and fractional sodium and potassium excretion decreased although there was hyperfiltration. The MSG group showed similar increase in blood pressure than the NaCl group, but nitric oxide excretion was significantly reduced. Although no increase in lipid peroxidation was verified, its observed alteration in the reduced glutathione/oxidized cycle and their enzymes GPx and GR. These changes were accompanied by alterations histological both glomerular as well as tubular level and by interstitial fibrosis with mononuclear cells accumulation.These results indicate that the addition of MSG in the diet decreases the excretion of Na, K and water with hyperfiltration. NaCl retention that leads to hypertension was accompanied by renal pathologic changes, intrarenal oxidative stress and reduction of nitric oxide excretion.     

Protective effect of Hesperidin and Tiger nut against Acrylamide toxicity in female rats

Phytochemicals that have antioxidant effect play important role in protection against several diseases in humans. This study was carried out to evaluate the efficacy of hesperidin and tiger nut against the early changes that may be related to the toxicity of acrylamide in female rats. 72 Sprague Dawley female rats were divided into six groups (12 rat/group): control group (I); hesperidin (HES) treated group (II); tiger nut (TN) treated group (III); Acrylamide (ACR) treated group (IV); HES-ACR treated group (V); and TN-ACR treated group (VI). There was a significant increase in the levels of serum carcino embryonic antigen (CEA), malondialdehyde (MDA), protein carbonyls (CO), ALT, AST, LDH, urea and creatinine while no significant changes of serum total sialic acid, progesterone (prog) and estradiol (E2) levels, and significant decreases of body weights, catalase (Cat) activity, superoxide dismutase (SOD) activity, reduced glutathione (GSH) level, and glutathione peroxidase (GSH-Px) activity of ACR treated group compared with the control. Our results suggested that supplementation of a diet with hesperidin provided antioxidant defense more significant than tiger nut against the toxicity of ACR in breast, liver and kidney tissues.     

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2 g/kg p.o. once only. After 24 h of APAP intoxication, animals were treated with three different doses of AuNPs (50 μg/kg, 100 μg/kg, 150 μg/kg) orally or silymarin at a dose of 50 mg/kg p.o., once only. Animals of all the groups were sacrificed after 24 h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.     

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

Comparison of long-term impact of immunosuppressants at therapeutic doses on hepatic function and histological changes in unilateral nephrectomized rats

Cyclosporine, tacrolimus and sirolimus are commonly used in renal transplant recipients to prevent rejection. Various adverse effects of these agents on the multiple organ system have been reported clinically. However, animal studies are necessary to determine and compare these effects on individual organ given the presence of multiple confounding factors and multi-pharmacy in clinical settings. In a physiologically and clinically relevant rat model of unilateral nephrectomy, the long-term impacts of commonly used immunosuppressants at doses equivalent to the therapeutic levels used for post-renal transplant patients on hepatic function and histological changes of the liver were examined. Cyclosporine induced significant hepatocellular injury, impairment of synthetic function of the liver, hyperbilirubinemia and cholestasis, and dyslipidemia accompanied by profound histological changes of hepatic structures on both light and electron microscopic examinations. On the other hand, neither tacrolimus nor sirolimus developed any hepatotoxic effects except for more remarkable dyslipidemia was observed in animals treated with sirolimus. Our study indicates that long-term administration of commonly used immunosuppressants has various impacts on biochemical parameters as well as histological alterations of the liver even at therapeutic levels. These data may therefore provide useful information for judicious selection of immunosuppressive agents based on different clinical settings.     

Oral acute toxicity study as well as tissues oxidative stress and histopathological disorders in edible camphor administered rats

In the South-western part of Nigeria, edible camphor (EC) infusions are used to treat pile, back pain, and erectile dysfunction, especially in preparation for sexual intercourse. We therefore carried out oral acute toxicity study, and then investigated the effects of various doses of EC on the activities of lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD), as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels in wistar rats. Oral LD₅₀ of EC was estimated to be 9487 mg/kg body weight. Based on this, thirty animals were divided into six groups of five rats each, and were orally administered various doses of EC (1, 2, 4, and 6 g/kg body weight) for seven days. Comparing all results with control, EC significantly increased serum LDH activity (4 and 6 g/kg), liver (6 g/kg) and kidney (4 and 6 g/kg) MDA levels, as well testis GSH levels (1 g/kg). CAT activities were significantly decreased in liver, kidney, and testis, and also lung GSH level by all the tested doses. For SOD, activities were significantly increased in liver and lung, but significantly decreased in kidney (2, 4, and 6 g/kg). Various pathological disorders were also seen following the various doses of EC administered, especially in liver, kidney and lung. Therefore, from our findings, it is evident that incessant, misuse or overconsumption of EC could lead to oxidative tissue damage in rats.     

Spontaneous unilateral renal dysplasia in a clinically healthy cynomolgus monkey (Macaca fascicularis)

Renal dysplasia is a congenital renal malformation characterized by disruption of normal renal development with asynchronous differentiation of nephrons, collecting ducts, and parenchyma and abnormal patterning of cortical and medullary tissues. The present article describes unilateral renal dysplasia discovered in a cynomolgus monkey from a routine toxicology study. The affected kidney was small and characterized by extensive interstitial fibrosis with the formation of fibromuscular collars around glomeruli and tubules, immature nephrons, and persistent mesenchyme encompassing few collecting ducts. The present case is remarkable in that there is a paucity of reports describing histopathologic findings of spontaneously occurring renal dysplasia in preclinical test species for use in large animal toxicity studies.     

大鼠30 min全脑缺血再灌注肾脏损伤及其机制研究

目的: 从血栓素(TXA₂)与前列环素(PGI₂)平衡失调和肿瘤坏死因子(TNF-α)的变化方面探讨老龄大鼠脑缺血再灌注肾脏损伤的发生机制。方法: 青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组, 观察大鼠全脑缺血30 min再灌注60 min后肾脏组织形态、肾内及血浆TXB₂、6-Keto-PGF_1α和肾内TNF-α含量的变化。结果: 青年和老龄模型组大鼠肾脏组织形态均出现明显的病理改变, 且老龄较青年更为严重。青年模型组血浆TXB₂/6-Keto-PGF_1α高于青年对照组和老龄模型组, 老龄对照组高于青年对照组。青年对照组肾脏组织TXB₂/6-Keto-PGF_1α低于老龄对照组和青年模型组, 老龄模型组高于青年模型组。老龄模型组肾组织TNF水平高于老龄对照组和青年模型组。结论: 以TXA₂占优势的TXA₂与PGI₂的平衡失调及TNF的增高与大鼠脑缺血再灌注肾脏损伤有关, 老龄大鼠脑缺血再灌注肾脏损伤的病理变化更明显。     

White Core of Cerebellum in Nicotine Treated Rats - A Histological Study

Although numerous studies explored the consequences of nicotine exposure on cerebellum and on its various layers, little research is focused on nicotine exposure on White core of cerebellum. In the present study, we assessed the effects of long-term nicotine exposure on White matter of cerebellum. Nicotine was administered for 60 days orally via cannula, using dose rate (5mg / day, 10 mg / day) to Male Drukrey rats. The results were compared to control adult rats, given vehicle in identical manner. After 60 days exposure, the cerebellum was removed and processed for histopathologic study. The results showed that long term nicotine treatment regime did result in significant loss of White core of cerebellum. These findings indicated that mature adult cerebellum is susceptible to the damaging effects of nicotine in depleting White core of cerebellum.     

Electrical stimulation of the brain stem in freely moving rats: I. Effects on behavior

Electrical stimulation (100 pulses/sec, 0.1 msec pulses) was applied to 129 sites located throughout the midbrain, pons and rostral medulla in freely moving rats, and behavioral effects recorded. Stimulation elicited a variety of motor patterns including head movements, turning, circling, forward locomotion (walking and running), freezing, chewing and fictive eating. Some of the behaviors appeared forced and unnatural, while others resembled normal movement. Some stimulation-bound behaviors appeared to be partially under environmental control. It is suggested that some behaviors elicited by stimulation of the brain stem may be due to relatively direct descending connections, but others may involve ascending inputs to the cerebral cortex as well.     

Renal and hepatic changes in the offspring of rats that received biological insecticides during pregnancy and lactation

Bacillus thuringiensis insecticides have been considered safe, being an alternative to the use of synthetic insecticides. However, studies have shown the effects of Bt Cry toxins on various organs, compromising their functions. The objective of this work was to test whether the administration of biological insecticides based on B. thuringiensis in pregnant rats will cause histopathological changes in the liver and kidneys, as well as in the levels of toxicity biomarkers, of their puppies in adulthood. Twenty rats, 90 days old, were used, divided into four groups: GC - Pregnant rats, GX - Pregnant rats that received XenTari®, GDi - Pregnant rats that received Dipel® and GDe - Pregnant rats that received deltamethrin. Insecticides were administered by gavage at a dosage of 1 mg/100 g/day (GX and GDi), and 2 mg/Kg/day (GDe) during pregnancy and lactation. In the animals of the groups whose matrices received the insecticides, there was a reduction in the levels of the biomarkers of toxicity alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, about the control group. The biological insecticides promoted histopathological changes in the liver, with the presence of portal vein, centrilobular and sinusoidal capillaries congestion, and in the kidney, presence of cortical congestion and reduction of the subcapsular space. Histochemical evaluation in the liver demonstrated a significant reduction in glycogen in the groups that received insecticides when compared to the control group, whereas for collagen fibers in both the liver and the kidneys, no differences were observed between the experimental groups. The morphometry of the liver revealed a significant reduction in the lobular parenchyma and an increase in the non-lobular parenchyma, and in the kidney, there was a reduction in the diameter and volume of the glomerulus and Bowman's capsule of the animals whose matrices received both biological and synthetic insecticides. Thus, it is concluded that the biological insecticides XenTari® and Dipel® in sublethal doses in pregnant rats promote changes in the liver and kidney of the offspring similar to the insecticide deltamethrin, which extend into adulthood.     

灯盏花素对糖尿病大鼠肝、肾组织氧化应激的影响

目的：探讨灯盏花素对糖尿病大鼠肝、肾组织氧化应激的影响。方法： 建立STZ诱导的糖尿病模型，随机分3组：正常对照组、模型组、灯盏花素给药组。8周后应用HE、油红O染色对肝组织、PAS染色对肾组织作病理检查。分光光度法检测肝、肾组织丙二醛(MDA)含量及抗氧化物酶活性。结果： HE染色显示模型组部分肝细胞脂肪变性，评分为1.54±0.65，灯盏花素给药组评分为0.55±0.43，差异高度显著(P<0.01)。油红O染色模型组肝组织评分为2.11±0.82，灯盏花素给药组为0.75±0.66，差异高度显著(P<0.01)。模型组大鼠肾重、肾重/体重、24 h尿白蛋白排泄率(AER)与肾小球面积(AG)、肾小球容量(VG) 及系膜区面积(AM)均明显增加，灯盏花素给药组这些改变减轻。灯盏花素给药组肝、肾组织MDA含量明显低于模型组(P<0.05，P<0.01)。超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及谷胱甘肽过氧化物酶(GSH-Px)活性明显高于模型组(P<0.05，P<0.01)。结论： 灯盏花素对糖尿病大鼠肝、肾组织有明显保护作用，其机制部分可能与抑制肝、肾组织氧化应激增加有关。     

肝门阻断再灌注对脑兴奋性氨基酸及受体mRNA表达的影响

目的： 探讨无肝期后的再灌注对脑组织兴奋性氨基酸（EAAs）及其受体mRNA表达的影响。方法：分别采用血气分析、高效液相色谱荧光检测和半定量RT-PCR方法，研究大鼠肝门阻断和假手术组再灌注6 h、12 h和24 h后门静脉电解质和pH、脑组织Glu、Asp含量以及大脑皮层中NMDAR mRNA的相对含量表达的差异，观察无肝期后再灌注损伤对肝外远隔脏器脑EAAs及NMDA受体mRNA表达的的影响。结果：肝门阻断期间门静脉pH显著降低，［K⁺］升幅超过1倍，但开放后逐渐恢复；［Ca²⁺］于再灌注后持续下降至12 h；脑皮层中的Glu和Asp再灌注后分别在6 h、24 h出现2个高峰［Glu:(349±145) μg·g^-1wt,(456±203) μg·g^-1wt vs (238±24) μg·g^-1wt,(225±59) μg·g^-1wt;Asp: (134±50) μg·g^-1wt,(166±50) μg·g^-1wt vs (99±24) μg·g^-1wt,(71±20) μg·g^-1wt］；NMDAR亚单位NR1mRNA的表达在再灌注后显著升高后逐渐下降［(1.63±0.06) μg·g^-1wt vs (1.18±0.05) μg·g^-1wt;(1.73±0.06) μg·g^-1wt vs (1.17±0.03) μg·g^-1wt］,而NR2B mRNA在12 h升高(1.75±0.04 vs 1.18±0.05)，2者24 h时均恢复至对照组水平。结论：肝门阻断后肝和肠道再灌注过程可启动神经突触前Glu大量释放和重吸收抑制，引起脑皮层EAAs的堆积，同时刺激NMDARmRNA的表达，通过Glu - NMDAR途径可能引发脑损伤。     

Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine

Carbofuran, a widely used carbamate pesticide, has been reported to cause neurotoxicity. However, the underlying mechanisms involved in carbofuran neurotoxicity are not well understood. The present study was envisaged to investigate the possible role of oxidative stress in carbofuran neurotoxicity and to evaluate the protective effects of N-acetylcysteine (NAC). Acetylcholinesterase activity was significantly inhibited in all the regions of brain after carbofuran exposure (1 mg/kg body weight, orally, for 28 days). NAC, on the other hand, was found to partially restore the activity of acetylcholinesterase in carbofuran treated animals. Carbofuran exposure resulted in increased lipid peroxidation (LPO) in brain regions accompanied by decreased levels of glutathione. NAC administration to the carbofuran exposed animals lowered LPO along with partial repletion in glutathione levels. Concomitantly, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were significantly decreased after carbofuran exposure, while no significant change in the activity of glutathione-S-transferase was observed. NAC treatment to carbofuran treated rats resulted in protective effect on the activities of these enzymes. Marked impairment in the motor function was seen following carbofuran exposure, which is evident by significant decrease in the retention time of the rats on rotating rods. Cognitive deficits were also seen after carbofuran exposure as indicated by the significant decrease in active avoidance response. NAC treatment significantly improved the carbofuran-induced neurobehavioral deficits. The results clearly demonstrate that carbofuran exerts its neurotoxic effects by accentuating oxidative stress and suggest neuroprotective role of NAC in carbofuran neurotoxicity.     

阿霉素前体脂质体对大鼠心肝毒性及对实验性肿瘤的作用

目的：研究阿霉素前体脂质体［ｄｏｘｏｒｕｂｉｃｉｎ（ＤＲ）,ｐｒｏｌｉｐｏｓｏｍｅ（ＰＬ）,ＤＲＰＬ］对大鼠心肝毒性及对荷瘤小鼠的抗肿瘤活性。方法：以酶活性变化为指标,结合病理组织学检查,观察药物对大鼠的心肝毒性及荷瘤小鼠的生命延长率和药物的抗肿瘤活性。实验动物分为ＤＲＰＬ组和ＤＲ组,其中２．００,１４０,０９８ｍｇ·ｋｇ１对应剂量观察药物对大鼠的毒性;４,２,１ｍｇ·ｋｇ１对应剂量观察药物的抗肿瘤活性。结果：与ＤＲＰＬ相比,ＤＲ可明显增加大鼠血清ＬＤＨ、ＣＫ、ＧＰＴ及ＧＯＴ的活性,ＤＲＰＬ对大鼠心肌细胞的损伤明显小于ＤＲ。相同剂量间相比ＤＲＰＬ延长腹水型小鼠移植瘤ＥＡＣ、Ｈｅｐｓ的存活天数明显高于ＤＲ。结论：ＤＲＰＬ对大鼠心肝毒性明显小于相同剂量的ＤＲ,ＤＲＰＬ不但保持了ＤＲ的抗肿瘤活性,而且有明显增效作用。     

Non heart-beating donors in England

When transplantation started all organs were retrieved from patients immediately after cardio-respiratory arrest, i.e. from non heart-beating donors. After the recognition that death resulted from irreversible damage to the brainstem, organ retrieval rapidly switched to patients certified dead after brainstem testing. These heart-beating-donors have become the principal source of organs for transplantation for the last 30 years. The number of heart-beating-donors are declining and this is likely to continue, therefore cadaveric organs from non-heart-beating donor offers a large potential of resources for organ transplantation. The aim of this study is to examine clinical outcomes of non-heart-beating donors in the past 10 years in the UK as an way of decreasing pressure in the huge waiting list for organs transplantation.     

Repeated Blood Collection in the Laboratory Mouse by Tail Incision-Modification of an Old Technique

Twenty years ago, tail incision for collecting serial blood samples from mice was introduced as a new technique. Despite a number of advantages over established methods, it has not become a frequently used technique. This report describes modifications of blood collection from mice by tail incision that allow obtaining rapid (1–1.5 min) serial blood samples (40–150 μl) from unanaesthetized laboratory mice. Evaluation of corticosterone concentrations in the blood plasma from repeated samples indicated that subsequent samples were unaffected by the procedure. Furthermore, histopathological examination demonstrated that repeated bleeding did not cause any lasting harm to the animals. Blood collection by tail incision may, therefore, be of particular interest for studies that attempt to relate physiological measures to behavioral responses in laboratory mice, and may contribute to the refinement of animal experimentation according to the principles of the Three Rs.     

Caffeic acid phenyl ester prevents cadmium intoxication induced disturbances in erythrocyte indices and blood coagulability,hepatorenal dysfunction and oxidative stress in rats

Here we investigated the protective role of caffeic acid phenyl ester (CAPE) on erythrocyte indices and osmotic resistance, blood coagulation, hepato-renal function and antioxidant status in cadmium (Cd) toxicity in rats. Cd intoxication was induced by intraperitoneal injection (i.p.) of cadmium chloride (1 mg/kg/day) for 21 days, and CAPE was daily given (10 μmol/kg; i.p.) also for 21 days. At day 22, blood samples, livers and kidneys were prepared for screening of: (1) erythrocyte indices: red blood cell (RBC) count, osmotic fragility, hemoglobin (HGB) concentration, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC); (2) blood coagulation tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) level; (3) serum levels of liver and kidney function biomarkers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, creatinine and blood urea nitrogen); (4) blood, liver and kidney levels of Cd; and (5) serum and hepato-renal concentrations of glutathione (GSH), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS). Cd intoxication significantly impaired hepato-renal function, prolonged PT and APTT, reduced FIB, decreased RBC count and osmoresistnacy as well as the values of HGB, HCT, MCV, MCH and MCHC. Interestingly, therapy with CAPE successfully eliminated Cd and significantly stabilized erythrocyte indices, blood coagulability and hepato-renal functional status in Cd-intoxication. Additionally, CAPE therapy significantly reversed the decreases in GSH and SOD, and the increases in TBARs that were induced by Cd intoxication. In conclusion, CAPE can represent a promising therapeutic agent in eliminating Cd and counteracting its hematological, hemostasis and hepatorenal toxic effects.     

异丙酚通过抑制JAK/STAT通路减轻肝冷缺血再灌注大鼠肾损伤

目的:探讨JAK/STAT信号通路在异丙酚减轻大鼠肝冷缺血再灌注后肾损伤中的作用。方法:SD大鼠随机分为4组(n=8):假手术组(sham组);肝冷缺血再灌注模型组(I/R组);异丙酚组(Pro组),于再灌注前5 min经右侧股静脉给予异丙酚20 mg·kg~(-1)·h~(-1)持续泵注30 min;JAK2抑制剂AG490组(AG490组),于建立模型前30 min腹腔注射AG490 10 mg/kg。再灌注6 h后处死大鼠,采集血样和肾组织标本,检测血清肌酐(Cr)、尿素氮(BUN)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的浓度及肾组织超氧化物歧化酶(SOD)和丙二醛(MDA)的水平;观察肾组织的病理学改变,并进行肾小管损伤评分;检测肾组织细胞凋亡并计算凋亡指数(AI);检测p-JAK2、p-STAT_1和p-STAT_3的蛋白水平。结果:与sham组比较,I/R组血清的Cr和BUN浓度、肾组织的MDA含量、肾小管损伤评分及AI均明显升高,SOD活性降低,p-JAK2、p-STAT_1和p-STAT_3的蛋白水平显著上调(P0.05)。与I/R组相比,Pro组和AG490组的血清BUN和Cr浓度、肾组织的MDA含量、AI和肾小管损伤评分降低,SOD活性升高,p-JAK2、p-STAT_1和p-STAT_3蛋白水平显著下调(P0.05)。结论:异丙酚可减轻肝冷缺血再灌注后肾损伤,其机制可能与抑制JAK/STAT信号通路激活有关。     

沙棘多糖抑制PERK/ATF4/CHOP通路缓解糖尿病大鼠胰岛素抵抗和肝肾功能损伤

目的　探究沙棘多糖（seabucthorn polysaccharide,SP）对糖尿病大鼠胰岛素抵抗和肝、肾功能损伤的影响。 方法　将大鼠随机分为对照组、链脲佐菌素（streptozocin,STZ）组、盐酸罗格列酮（rosiglitazone,RSG）组（4 mg·kg-1·d-1）和SP低、中、高剂量组（50、100、200 mg·kg-1·d-1）,除对照组外其余大鼠均建立为Ⅱ型糖尿病模型。药物处理后,通过天平、血糖仪、Elis检测大鼠体重、双侧肾重、空腹血糖和胰岛素水平,计算肾肥大指数、胰岛素抵抗指数;Elisa检测HbA1C、脂联素;生化分析仪检测TG、TC、LDL-C、HDL-C、PRO、Scr、BUN水平;油红O染色、HE染色观察肝脂肪沉积情况和肾组织形态;Western Blot检测PERK/ATF4/CHOP通路活化水平。 结果　与STZ组相比,SP中、高剂量组大鼠体重、脂联素、HDL-C升高（P<0.05）,血糖、胰岛素抵抗指数、肾肥大指数、HbA1C、血浆胰岛素、TG、TC、LDL-C、PRO、Scr、BUN水平下调（P<0.05）,缓解大鼠肝脂质沉积和肾损伤,且抑制PERK/ATF4/CHOP通路活性。 结论　沙棘多糖可缓解糖尿病大鼠胰岛素抵抗和肝、肾功能损伤,其机制可能与抑制PERK/ATF4/CHOP通路活性有关。