Codonopsis javanica root extracts attenuate hyperinsulinemia and lipid peroxidation in fructose-fed insulin resistant rats

From ancient times, Dǎngshēn (Codonopsis javanica) has been used in Chinese traditional medicine. In this study we investigated the anti-hyperinsulinemia and antioxidant properties of C. javanica root extracts in a rat model of insulin resistance (IR), induced by chronic fructose feeding. Twenty-four Sprague–Dawley rats were randomized into control, fructose-treated (10%, w/v), and fructose then C. javanica (Fru + Cod)-treated groups. After 8 weeks fructose feeding, increased fasting serum insulin levels (2.6 ± 0.45 μg/L) and insulin area under the curve confirmed the IR (p < 0.001). However, C. javanica treatment to fructose-fed rats significantly attenuated the hyperinsulinemia with correspondingly improved glucose tolerance. Weight gain in Fru + Cod group was comparably (p < 0.01) lower than in the fructose-fed group. Furthermore, IR-induced increased hepatic lipid peroxidation, as demonstrated by elevated malondialdehyde levels, were significantly (p < 0.001) alleviated by C. javanica treatment. These findings reveal that chronic fructose intake may facilitate IR and oxidative damage, which could be eradicated by improved antioxidant status. Accordingly, we found that C. javanica treatment significantly improved the antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase and glutathione reductase in the liver. These findings that fructose-induced hyperinsulinemia and associated oxidative stress could be attenuated by C. javanica root extracts.     

Oxidative stress induced by Cremophor EL is not accompanied by changes in NF-kappaB activation or iNOS expression

The effects of polyoxyethylenglycerol triricinoleate 35 (Cremophor EL, CrEL) on markers of oxidative stress, nuclear factor kappa B (NF-kappaB) activation and inducible nitric oxide synthase (iNOS) expression were studied in the liver of male Wistar rats. Animals were randomly divided into three groups. Group Cr1 received, i.p., CrEL at 0.046ml/kg daily for 7 days, group Cr2 received CrEL at 0.33ml/kg and the controls were injected with CrEL vehicle (saline solution with 25% ethanol). Both alanine transaminase (ALT) and aspartate transaminase (AST) serum activities were significantly increased in the Cr2 group (+16% and +25%, respectively). AST activity was also higher in the Cr1 group when compared to control animals (+20%). The cytosolic concentration of thiobarbituric acid reactive substances (TBARS) increased in both groups of rats receiving CrEL (Cr1: +24%; Cr2: +33%). Reduced glutathione (GSH) concentration was not significantly modified at any of the CrEL doses, but both the hepatic concentration of oxidised glutathione (GSSG) (Cr1: +37%; Cr2: +84%) and the GSH/GSSG ratio (Cr1: -21%; Cr2: -45%) were significantly modified. CrEL induced no significant NF-kappaB activation, changes in p50 and p65 NF-kappaB subunits or induction of iNOS protein. Data obtained indicate that although high doses of CrEL cause oxidative stress, this is not enough to induce changes in NF-kappaB activation or iNOS expression.     

Protective effects of early administration of alpha-lipoic acid against lipopolysaccharide-induced plasma lipid peroxidation

Lipopolysaccharide (LPS), called endotoxin, is a major component of Gram-negative bacteria cell wall. LPS stimulates the synthesis and release of several metabolites from mammalian phagocytes which leads to fulminant systemic inflammation (endotoxic shock). Among LPS-induced metabolites, reactive oxygen species are considered to play crucial role in the pathogenesis of endotoxic shock via oxidative stress generation. In this study, the effect of early administration of antioxidant alpha-lipoic acid (LA) on plasma lipid peroxidation and total antioxidant blood capacity was evaluated in endotoxic shock in rats. Lipid peroxidation was measured as plasma thiobarbituric acid reactive substances (TBARS) levels, while total blood antioxidant capacity was assessed as ferric reducing ability of plasma (FRAP). The endotoxic shock was induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg, iv) in anesthetized rats. Then, 30 min later, animals were treated intravenously (iv) with LA at 60 mg/kg. After 5 h observation animals were killed and blood from heart was taken for TBARS and FRAP measurements. LPS injected to saline-pretreated animals resulted in development of oxidative stress indicated by significant increases in plasma TBARS and significant decrease in total antioxidant capacity of plasma. Conversely, LA injected to saline pretreated animals caused an increase in FRAP values and the decrease in TBARS levels. The administration of LA 0.5 h after LPS challenge resulted in an increase in FRAP values and decrease in plasma lipid peroxidation as compared to LPS group. Moreover, the levels of TBARS and FRAP in LPS + LA group were similar to those observed in LA group. In conclusion, our present study demonstrates that early treatment with LA significantly protects against endotoxin-induced oxidative stress in rats.     

基于Keap1-Nrf2/ARE信号通路研究牛磺酸对胰岛素抵抗模型大鼠氧化应激的影响

目的 通过研究牛磺酸对胰岛素抵抗大鼠模型的血糖、血脂、氧化应激指标以及Keap1-Nrf2/ARE信号通路重要靶点的影响,并探讨其分子调控机制。方法 建立胰岛素抵抗SD大鼠模型,测定连续灌胃给药7周后正常组、模型组、二甲双胍组、牛磺酸高剂量组以及牛磺酸低剂量组的空腹血糖（fasting blood glucose,FBG）、空腹胰岛素、甘油三酯（triglyceride,TG）、总胆固醇（total cholesterol,TC）、高密度脂蛋白、低密度脂蛋白,计算胰岛素抵抗指数;采用酶联免疫吸附试验法测定肝组织中超氧化物歧化酶（superoxide dismutase,SOD）、丙二醛（malondialdehyde,MDA）,运用RT-PCR技术检测肝组织中Nrf2、Keap1、HO-1、NQO1 mRNA的表达量。结果 给药7周后,与模型组比,牛磺酸高剂量组胰岛素抵抗大鼠FBG、空腹胰岛素降低（P<0.05）,血清TC、TG水平也降低（P<0.05）;大鼠肝组织的SOD升高、MDA降低（P<0.05）;肝组织中HO-1、NQO1、Nrf2的mRNA水平上调（P<0.05）, Keap1 mRNA水平下调（P<0.01）。结论 牛磺酸可调节糖尿病大鼠的血糖、血脂,改善模型大鼠氧化应激状态,减轻胰岛素抵抗,可能与其调控Keap1-Nrf2/ARE信号通路中关键基因表达从而改善氧化应激有关。     

Changes in redox ratio and protein glycation in precataractous lens from fructose-fed rats: effects of exogenous L-carnitine

1. Rats fed high dietary fructose are documented to form an acquired model of insulin resistance. The present study measured the effects of administration of L-carnitine (CA) on lens protein glycation, oxidative stress and redox homeostasis in rats fed a high-fructose diet. 2. Animals were divided into four groups: (i) an untreated control group (fed starch diet); (ii) an untreated fructose-group (fed a high-fructose diet); (iii) a CA-treated (300 mg/kg per day), fructose-fed group; and (iv) a CA-treated, starch-fed group. After 60 days treatment, lenses were dissected and multiple oxidative stress markers, glycation of proteins and the ratio of oxidized to reduced glutathione (GSSG/GSH) were determined. 3. A significant decline in enzyme and non-enzyme anti-oxidants and an increase in lipid peroxidation products, protein oxidation, protein glycation, GSSG/GSH ratio and aldehyde formation were observed in lens samples obtained from fructose-fed rats. Administration of CA to fructose-fed rats significantly attenuated oxidative damage and protein glycation and returned levels of anti-oxidants to near those seen in the control group. 4. The results of the present study indicate that dietary fructose disturbs lens integrity and exogenous CA may safeguard the lens by preventing glycation and oxidative stress.     

Effects of the K+ channel opener KRN4884 on the cardiovascular metabolic syndrome model in rats

We examined the effects of the potassium channel opener KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ) on cardiovascular metabolic syndrome (i.e., syndrome X), in rats. High-fructose diet rats developed hypertension, hypertriglyceridemia, increased total cholesterol/HDL (high-density lipoprotein)-cholesterol ratio, and hyperinsulinemia, KRN4884 (0.3-3.0 mg/kg, twice a day for 14 days, p.o.) alleviated the risk factors in fructose-fed rats. Furthermore, fructose-fed rats exhibited impairment of glucose tolerance and excess insulin secretion when loaded with glucose orally. Treatment with KRN4884 (1.0 mg/kg, twice a day for 14 days, p.o.) improved the glucose intolerance and inhibited hypersecretion of insulin in the glucose-loaded, fructose-fed rats. In contrast, KRN4884 (0.3-1.0 mg/kg, twice a day for 10 days, p.o.) did not affect serum triglyceride, cholesterol, glucose, or insulin concentrations in normal rats. LPL (lipoprotein lipase) activities in skeletal muscle and adipose tissue, and HTGL (hepatic triglyceride lipase) activity in liver were measured after administration of KRN4884 or vehicle twice a day for 14 days in fructose-fed rats. KRN4884 caused a significant increase in LPL activity in muscle and tended to increase LPL activity in adipose tissue in fructose-fed rats. HTGL was decreased in fructose-fed rats as compared with normal controls and was unaffected by KRN4884. These findings suggested that KRN4884 enhances insulin sensitivity and LPL activity, which are related to glucose and lipid metabolism and may be useful for the treatment of syndrome X.     

Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats

1. Oxidative stress is believed to be a pathogenetic factor in the development of diabetic complications. In the present study, we investigated the ethanolic extract of the aerial parts of Andrographis paniculata for antihyperglycaemic and anti-oxidant effects in normal and streptozotocin-induced type I diabetic rats. 2. Normal and diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water), metformin (500 mg/kg bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days. 3. At the end of the 14 day period, the extract, like metformin, significantly increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and serum glucose in normal rats. Levels of liver and kidney thiobarbituric acid-reactive substances (TBARS) were significantly increased (P < 0.0001, P < 0.01, respectively), while liver glutathione (GSH) concentrations were significantly decreased (P < 0.005) in vehicle-treated diabetic rats. Liver and kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005, respectively), whereas liver GSH concentrations were significantly higher (P < 0.05) in extract- and metformin-treated diabetic rats compared with vehicle-treated diabetic rats. Andrographis paniculata significantly decreased kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly lower in vehicle-treated diabetic rats compared with vehicle-treated normal rats. The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH-Px activity in diabetic rats. The extract and metformin did not produce significant changes in the activity of these anti-oxidant enzymes in normal rats. 4. Our results show that oxidative stress is evident in streptozotocin-diabetic rats and indicate that the ethanolic extract of A. paniculata not only possesses an antihyperglycaemic property, but may also reduce oxidative stress in diabetic rats.     

二甲双胍对糖尿病大鼠肝脏葡萄糖-6-磷酸酶表达的影响

目的：探讨二甲双胍抑制肝糖输出，减轻肝脏胰岛素抵抗的分子学机制。方法：建立糖尿病大鼠模型并将之分为正常对照组、糖尿病组、低剂量二甲双胍干预组、高剂量二甲双胍干预组，饲养2周后取出肝脏，以半定量RT-PCR方法测定肝脏葡萄糖-6-磷酸酶（G6Pase）mRNA的表达，蒽酮比色法测定肝脏糖原含量。结果：（1）糖尿病组肝脏G6Pase催化亚基（P36）及转运亚基（P46）mRNA的灰度高于正常对照组（P〈0．05），而肝脏糖原含量低于正常对照组（P〈0．05）。（2）二甲双胍可以明显减少肝脏G6Pase mRNA表达并增加肝糖原含量（P〈0．05），且呈剂量依赖性。结论：二甲双胍能够抑制糖尿病状态下肝脏G6Pase催化亚基及转运亚基mRNA表达，使得6-磷酸葡萄糖向葡萄糖的转化减少，从而减少肝糖输出，达到减轻胰岛素抵抗的作用。     

Noradrenaline and angiotensin II modify vascular prostanoid release in fructose-fed hypertensive rats

1 A fructose-enriched diet induces hypertension, metabolic alterations and insulin resistance in rats, resembling human metabolic syndrome. Previously, we found that prostanoid production was altered in fructose-fed rats. 2 This study analysed the effects of incubation with noradrenaline (NA) and angiotensin II (Ang II) on prostanoid release in mesenteric vascular beds from control and fructose-fed rats. Animals which received fructose solution (10% w/v) for 22 weeks showed higher systolic blood pressure and triglyceridaemia. 3 In controls, NA increased 6-keto-prostaglandin (PG) F(1)alpha (prostacyclin metabolite) and thromboxane (TX) production. Ang II increased only TX release. In fructose-fed animals, NA increased 6-keto-PG F(1)alpha and TX. PGF(2)alpha (vasoconstrictor) was also elevated. Ang II also increased PGF(2)alpha and PGE(2) levels. 4 In conclusion, in fructose rats Ang II in vitro stimulates a vasoconstrictor prostanoid not stimulated in controls. This could be related to the observed in vivo blood pressure increase. In fructose-fed animals, NA and Ang II also augment vasodilator prostanoids, suggesting a compensatory mechanism because of long-term hypertension.     

胰岛素强化治疗对2型糖尿病大鼠氧化应激的影响研究

目的探讨胰岛素强化治疗对2型糖尿病(T2DM)大鼠氧化应激的影响,为临床胰岛素强化治疗提供理论依据。方法将36只Wistar大鼠随机分为正常对照组(NC组,n=12)和高脂组(HF组,n=24),将HF组大鼠造成T2DM模型后再随机分为2个亚组,即糖尿病对照组(DC组,n=12)和胰岛素治疗组(IT组,n=12)。IT组大鼠皮下注射胰岛素,NC组和DC组大鼠皮下注射等容积0.9%氯化钠溶液,疗程4周,比较3大鼠实验前后血清及肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽转移酶(GSM)水平。结果 IT组血清及肝组织中SOD、GSM较DC组升高,差异有统计学意义(P<0.05);DC组较NC组降低,差异有统计学意义(P<0.01);IT组较NC组降低,差异有统计学意义(P<0.05)。IT组血清及肝组织中MDA较DC组降低,差异有统计学意义(P<0.05);DC组较NC升高,差异有统计学意义(P<0.01);IT组较NC组升高,差异有统计学意义(P<0.05)。结论 T2DM大鼠存在脂质过氧化水平升高及抗氧化酶活性下降,胰岛素强化治疗可减轻T2DM大鼠的氧化应激损伤,其机制与改善血脂代谢紊乱,减轻脂毒性有关。     

Tetrahydrobiopterin prevents endothelial dysfunction and restores adiponectin levels in rats

Oxidative stress induces endothelial dysfunction and hypoadiponectinemia. We previously reported that supplementation with tetrahydrobiopterin (BH4), one of the most potent naturally occurring reducing agents and an essential cofactor of enzymatic NO synthase (NOS), ameliorates endothelial dysfunction and reverses hypoadiponectinemia as a result of oxidative stress in rats. To further confirm this hypothesis, we investigated the effects of treatment with BH4 on endothelium-dependent relaxation and adiponectin levels during oxidative stress in fructose-fed rats, which provide an animal model for the metabolic syndrome. Ingestion of a fructose diet for 8 weeks significantly impaired endothelium-dependent arterial relaxation in aortic strips and decreased plasma adiponectin levels, as well as adiponectin mRNA levels within adipose tissue. However, oral supplementation with BH4 (10 mg/kg day) over the final 4 weeks leads to a significant partial reversal of impaired endothelium-dependent arterial relaxation, as well as normalization of plasma adiponectin and fat adiponectin mRNA levels. Moreover, BH4 treatment of the fructose-fed rats significantly reduced the lipid peroxidation content of aorta, heart, liver, and kidney tissues, which were increased in fructose-fed rats. This effect of BH4 treatment may be due to its function as a cofactor for eNOS, as well as its anti-oxidative effects. Thus, BH4 might show promise for the treatment of oxidative stress-induced disorders, including the metabolic syndrome.     

二甲双胍对舒必利、利培酮所致大鼠糖脂代谢紊乱的影响

目的探讨二甲双胍防治抗精神病药舒必利、利培酮所致的大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着的效果。方法大鼠第1~4天予舒必利25 mg·kg-1·d-1或利培酮0.05 mg·kg-1·d-1灌胃,从第5日起舒必利加至50 mg·kg-1·d-1或利培酮加至0.1 mg·kg-1·d-1,2周后加用二甲双胍100 mg·kg-1·d-1,总共给药周期为8周;取基线,3 d,1周,2周,4周,6周,8周7个时间点,称取大鼠体质量,测空腹血糖(fasting blood-glucose,FBS)及餐后2 h血糖(2-hour post-meal blood glucose,2h PBG);于实验第8周末检测血清果糖胺(fructosamine,FA)、胰岛素(insulin,IRS)水平血清胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)及高密度脂蛋白(high density lipoprotein cholesterol,HDL-C),并取大鼠肝脏进行常规HE染色。结果各时间点二甲双胍组与正常对照组各相关指标差异无统计学意义;与正常对照组比较,服用舒必利组、利培酮组大鼠在第6周、8周末体质量、2h PBG、INS、FA升高(P<0.05),8周末TC、TG、HDL-C升高(P<0.05),LDL-C降低(P<0.05),而舒必利与利培酮组比较,上述指标差异无统计学意义;舒必利或利培酮合用二甲双胍的大鼠6周及8周末体质量、2h PBG、INS、FA较单独使用舒必利或利培酮的大鼠更低(P<0.05),8周末TC、TG、HDL-C更低(P<0.05),LDL-C较高(P<0.05)。肝脏病理示舒必利及利培酮组大鼠肝细胞形态紊乱,血管周围见多量白色脂肪浸润细胞,且在距离血管较远的肝细胞也可见到脂质沉着;舒必利或利培酮合用二甲双胍的大鼠肝细胞形态整齐,血管周围及血管较远白色脂肪浸润细胞明显少于舒必利及利培酮组。结论抗精神病药舒必利、利培酮可引起大鼠体质量增加、血糖升高、糖耐量异常、脂代谢紊乱及肝脏脂质沉着,二甲双胍能有效地防治舒必利、利培酮所致的大鼠体质量增加及糖脂代谢紊乱,并能减轻肝脏脂质沉着。     

Rosiglitazone increases extravasation of macromolecules and endothelial nitric oxide synthase in skeletal muscles of the fructose-fed rat model

Reduced extravasation of macromolecules in skeletal muscle has recently been documented in the fructose-fed rat model, corroborating a hypothesis that a functional obliteration of muscle regional microcirculation might lead to hypertension and restrict access of nutrients and hormones to their target cells. The goal of this study was to assess the impact of a treatment with rosiglitazone on the reduced muscle vasopermeability observed previously in the fructose-fed rat model. Fructose-fed Sprague-Dawley rats were gavaged with rosiglitazone (10 micromol kg(-1) per day; n = 21) or the vehicle only (n = 19) for 3 consecutive weeks before assessing the extravasation of Evans Blue (EB) dye in vivo in distinct muscle groups. Relative to control group, rosiglitazone reduced mean arterial blood pressure (Delta = -16.7%, P < 0.001), plasma insulin (Delta= -39.1%, P < 0.05) and plasma triglyceride (Delta= -32.8 %, P < 0.01) concentrations in a significant manner. Plasma VEGF concentrations were significantly lower in the rosiglitazone-treated animals compared to the control animals (32.7 +/- 0.8 pg ml(-1) versus 46.1 +/- 1.2 pg ml(-1), P < 0.001). While no changes were observed in the lungs or the kidneys, fructose-fed rats treated with rosiglitazone had a 30-50% increase (P < 0.005) in the extravasation of EB regardless of the skeletal muscle group studied (rectus femoris, soleus, gastrocnemius lateralis, vastus lateralis and tibialis cranalis). In homogenates of skeletal muscles (vastus lateralis) of fructose-fed rats, rosiglitazone resulted in a significant increase in NO synthase (NOS) activity (Delta = +41.9 %, P < 0.003) as well as endothelial NOS immunoreactive mass (Delta = +37.8 %, P < 0.01) compared to the control animals. There was no change in the immunoreactive level of the nNOS isoform, the most abundant muscle isoform, or in the immunoreactive levels of VEGF. In conclusion, rosiglitazone appears to restore a vascular dysfunction previously documented in the skeletal muscle microcirculation, as evidenced by improved skeletal muscle vasopermeability and upregulation of the muscle endothelium-NO system in the fructose-fed rat model. These effects on muscle per se might also result in a partial improvement of the insulin resistance phenomenon by improving the distribution of nutrients and insulin to skeletal muscle. This effect appears to be independent of circulating levels of VEGF since changes in plasma concentrations of this permeability factor were lower in the rosiglitazone-treated group.     

Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats

The study determines the effect of genistein on inflammatory status and expression of nuclear factor-kappa B (NF-κB p65), transforming growth factor-β1 (TGF-β1) and receptor for advanced glycation end products (RAGE) in kidney of fructose-fed rats. Adult male Wistar rats were fed a diet containing either starch or fructose as the source of carbohydrate. Fifteen days later, after confirming the development of insulin resistance in fructose-fed rats, the rats in each dietary group were divided into two and treated with either genistein (1 mg/kg/day) in 30% dimethylsulfoxide (DMSO) or 30% DMSO alone for the next 45 days. The expression of NF-κB P(65), TGF-β1 and RAGE, histochemical localization of α-smooth muscle actin (α-SMA), levels of tumour necrosis factor-α (TNF-α) and interleukin-6(IL-6) and ultrastructural analysis were performed at the end of the experimental period. Fructose-fed rats displayed inflammatory changes in kidney. Increased expression of TGF-β1 and RAGE in cytosol and NF-κB p65 in nuclear fraction were observed. α-SMA expression was higher in fructose-fed rat kidney. Proliferation of connective tissue was evident from increased collagen deposition in perivascular and intraglomerular regions. Administration of genistein to fructose-fed rats reduced inflammation, fibrogenesis and NF-κB activation. Genistein also mitigated the structural changes such as basement membrane thickening, reduction in podocyte number and loss of glomerular filtration barrier integrity. These findings suggest that genistein prevents inflammation, fibrosis and early nephropathic changes in fructose-fed insulin resistant rats secondary to the attenuation of NF-κB activation.     

不同治疗方案对初诊2型糖尿病患者的缓解率评价

目的探讨不同治疗方案治疗初诊2型糖尿病患者的缓解率。方法选择65例初诊2型糖尿病患者,随机分成"胰岛素"组、"胰岛素+二甲双胍"组、"胰岛素+二甲双胍+吡格列酮"组,定期监测血糖,调整用量,计算并比较各组患者糖尿病缓解率;同时,研究与之相关的影响因素。结果治疗后,总缓解率为43.1%,"胰岛素+二甲双胍+吡格列酮"组缓解率为57.1%。根据结果,分为"缓解组"与"未缓解组",缓解组病程比未缓解组短(P<0.05),缓解组BMI明显>未缓解组(P<0.01),两组治疗前空腹血糖比较差异无统计学意义(P>0.05)。结论对于初诊2型糖尿病患者,"胰岛素+二甲双胍+胰岛素增敏剂"可能是更好的治疗方式,且病程短、BMI值高的患者更容易达到缓解。     

牛磺酸干预对糖尿病大鼠糖脂代谢及氧化应激的影响

目的：探讨牛磺酸对2型糖尿病大鼠糖脂代谢和氧化应激的影响。方法：通过喂食SD大鼠高糖高脂饲料合并腹腔注射35 mg·kg^-1链脲佐霉素（STZ）制备2型糖尿病大鼠模型。将造模成功的大鼠随机分为模型组、二甲双胍组（400 mg·kg^-1）、牛磺酸低剂量组（400 mg·kg^-1）和牛磺酸高剂量组（600 mg·kg^-1），连续灌胃给药7周。测定各组大鼠的血糖（FBG）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL）、低密度脂蛋白胆固醇（LDL）和极低密度脂蛋白胆固醇（VLDL），血清胰岛素（FINs），并计算胰岛素抵抗系数（IRI）；取肝、肾组织匀浆液，测定超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物（GPH-Px）、过氧化氢酶（CAT）、总抗氧化能力（T-AOC）含量。对氧化应激与糖脂代谢指标进行主成分分析。结果：牛磺酸高、低剂量组均具有降低血糖、TC、TG的作用，对VLD、HDL有一定影响，但无统计学差异（P>0.05）。牛磺酸高剂量组可升高肝组织GSH、T-AOC（P<0.05），降低MDA（P<0.05），也可降低肾组织MDA（P<0.05）。牛磺酸低剂量组可升高肾组织GSH，T-AOC（P<0.05）。主成分分析显示，氧化应激水平与糖脂代谢密切相关。结论：牛磺酸可改善2型糖尿病大鼠的氧化应激损伤，调节糖尿病大鼠的糖脂代谢。     

小檗碱对胰岛素抵抗大鼠糖脂代谢影响的研究

目的研究小檗碱对胰岛素抵抗大鼠糖脂代谢相关指标的影响及其酶学机制。方法选用雄性Wistar大鼠,以高脂高热量饲料喂养8周,复制胰岛素抵抗大鼠模型,造模成功后随机分成模型组、小檗碱组、二甲双胍组,各组干预4周,同时设置健康对照组;比较各组葡萄糖耐量试验(GTT)各时间点血糖水平、总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、胰岛素敏感性指数(ISI)、肝脏葡萄糖激酶(GK)活性的差异。组间均数比较采用方差分析和LSD-t检验。结果与模型组比较,小檗碱组餐后60min血糖水平下降[分别为(7.2±1.4)mmol/L,(8.0±1.2)mmol/L,P<0.05],FFA水平下降[分别为(258±29)mmol/L,(479±34)mmol/L,P<0.05],ISI增强[分别为(-4.9±0.3),(-5.4±0.4),P<0.05],GK活性增强[分别为(13.6±1.7),(5.6±0.8),P<0.05];二甲双胍阳性对照组取得类似结果。结论小檗碱能调节胰岛素抵抗大鼠的糖脂代谢水平,增强胰岛素敏感性;其调节糖代谢机制可能与提高GK活性水平有关。     

Preventive effect of embelin from embelia ribes on lipid metabolism and oxidative stress in high-fat diet-induced obesity in rats

A high-fat diet (HFD) results in hyperlipidemia and an increase in oxidative stress. The purpose of this study was to investigate the preventive effect of embelin against hyperlipidemia and oxidative stress in HFD-induced obesity in rats. Male Wistar rats aged 12 weeks (150-200 g) were fed with an HFD for a period of 28 days to induce experimental obesity. HFD-induced obese rats were treated with embelin (50 mg/kg) or orlistat (10 mg/kg) for 21 days. A range of parameters were tested including body weight gain, body mass index (BMI), blood pressure, visceral fat pad weights, serum levels of glucose, insulin, leptin, apolipoprotein B (ApoB), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Twenty-one days of embelin (50 mg/kg) treatment produced effects similar to orlistat in reducing body weight gain, blood pressure, visceral fat pad weight, serum lipid levels, as well as coronary artery risk and atherogenic indices of HFD-fed rats. Embelin treatment also lowered the serum levels of glucose by 24.77 %, insulin by 35.03 %, and leptin by 43.39 %. Furthermore, embelin treatment significantly (p < 0.01) decreased the hepatic TBARS levels, while increasing the SOD, CAT, and GSH levels in obese rats. The present study indicated the preventive effect of embelin in HFD-induced obesity and its related complications. Embelin could be valuable in the development of new drug therapies to prevent obesity, hyperlipidemia, and oxidative stress.     

Influence of prenatal waterpipe tobacco smoke exposure on renal biomarkers in adult offspring rats

Background: Waterpipe tobacco smoke (WTS) is a popular form of tobacco consumption. Prenatal exposure to cigarette smoke altered kidney function and oxidative stress balance in offspring. However, the effect of prenatal WTS exposure on kidney function parameters, blood pressure and oxidative stress in adult offspring rats were unknown.

Methods: Pregnant Wister rats were exposed to either WTS for 2?hours per day utilizing a whole body exposure system or fresh air from day 0 of gestation to day 21. Systolic blood pressure, histological analysis of kidney, kidney function biomarkers [angiotensin converting enzyme (ACE), angiotensin I, angiotensin II, urea nitrogen, creatinine and albumin], and oxidative stress biomarkers (glutathione peroxidase (GPx), catalase and thiobarbituric acid reactive substances (TBARS)) were measured in male- and female- offspring rats on week 20.

Results: Prenatal exposure to WTS significantly decreased kidneys’ weight and glomeruli area (p?<?0.05) in offspring rats. Prenatal WTS exposure increased blood pressure in offspring rats (p?<?0.05). Further, prenatal WTS exposure increased the level of urine albumin (p?<?0.05) in offspring rats. Prenatal WTS exposure increased the level of ACE and angiotensin I (p?<?0.05) in female offspring rats. Prenatal WTS exposure increased the level of TBARS (p?<?0.05) in female offspring rats and there was a trend of decreased activity of GPx in male and female offspring rats, but was not significant (p?>?0.05).

Conclusions: Maternal WTS exposure during pregnancy resulted in detrimental effects on the renal system as indicated by altered kidney parameters and function, increased systolic blood pressure and oxidative stress in adult offspring rats.