Aframomum melegueta prevents the ejaculatory complications of propylthiouracil-induced hypothyroidism in sexually experienced male rats: Evidence from intravaginal and fictive ejaculations

ObjectiveHypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract (AE) and methanolic extract (ME) of A. melegueta on the ejaculatory function of hypothyroid male rats.MethodsForty sexually experienced male rats were partitioned into 8 groups (5 rats per group) and treated for 28 d as follows: Group 1, Control; Group 2, propylthiouracil (PTU, 10 mg/kg) + distilled water (DW, 10 mL/kg); Group 3, PTU + 5% Tween 80 (10 mL/kg); Group 4, PTU + bromocriptine (6 mg/kg); Group 5, PTU + AE (20 mg/kg); Group 6, PTU + AE (100 mg/kg); Group 7, PTU + ME (20 mg/kg), and Group 8, PTU + ME (100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time (ELT) and post-ejaculatory interval (PEI) for 1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected. Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings, blood was collected through the catheterization of abdominal artery and plasma was used for thyroid-stimulating hormone (TSH), prolactin and testosterone assays.ResultsPTU-induced hypothyroidism was characterized by a significant elevation (P < 0.001) of plasmatic TSH and prolactin levels, but a decline (P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone (AE, 100 mg/kg, P < 0.01; ME, 100 mg/kg, P < 0.05) and decreased prolactin (AE, 100 mg/kg, P < 0.05; ME, 20 mg/kg, P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered (P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT (P < 0.05) and PEI (P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly (P < 0.05) alleviated in plant extract-treated groups.ConclusionThis study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.     

Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract

ObjectiveThe present study investigated the anticataract activity of a novel isoflavonoid, isolated from stem bark of Alstonia scholaris, against fructose-induced experimental cataract.MethodsThe bioactivity of fractions extracted from A. scholaris, an isolated isoflavonoid (ASII) was screened using in vitro (goat lens) and in vivo (albino rats) experimental cataract models. For the in vivo evaluation, albino rats (12–15 weeks old) were divided into five groups (n = 6). Group I (normal) received 0.3% carboxymethyl cellulose solution (10 mL/[kg·d], p.o.). Group II (control) received 10% (w/v) fructose solution in their drinking water. Groups III–V received ASII at three different doses, 0.1, 1.0 and 10 mg/(kg·d), concurrently with 10% (w/v) fructose solution. Treatment was given daily for 8 consecutive weeks. During the protocol, systolic blood pressure, diastolic blood pressure, blood glucose level and lenticular opacity were monitored at 2-week intervals. Pathophysiological markers (catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and malondialdehyde) in eye lenses were examined at the end of the 8-week treatment period.ResultsThe results of in vitro study showed that A. scholaris extract and the active fraction (A₃) reduced the lenticular opacity as compared to toxic control group. The in vivo study showed that 8-week administration of ASII (0.1, 1.0 and 10 mg/[kg·d], p.o.) led to significant reduction in blood pressure and blood glucose level and retarded the initiation and evolution of cataractogenesis, compared to the fructose-induced cataract model control. Additionally, ASII treatment led to significant improvement in lens antioxidants (catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione) and decreased lens malondialdehyde, compared to the control group (group II).ConclusionResults revealed that administration of ASII played a crucial role in the reduction of cataract formation in diabetic and hypertensive models.     

补肾中药有效成分对SAMP8小鼠海马APP及PS1基因表达的影响

[目的]观察补肾中药有效成分淫羊藿苷、补骨脂素、齐墩果酸对6月龄SAMP8小鼠淀粉样前体蛋白(APP)及早老素-1(PS1)基因表达的作用,为补肾中药防治老年性痴呆提供实验依据。[方法]选择6月龄健康雄性SMAP8小鼠40只,随机分为模型组、淫羊藿苷组、补骨脂素组、齐墩果酸组,每组10只。另取10只SAMR1小鼠作为对照组。治疗组分别给予淫羊藿苷、补骨脂素、齐墩果酸灌胃治疗(浓度为淫羊藿苷20 mg/kg,齐墩果酸、补骨脂素各50 mg/kg),每日1次,每次0.3 mL,连续灌胃4周。对照组与模型组均给予等量生理盐水灌胃。4周后应用逆转录-聚合酶链反应(RT-PCR)方法检测海马组织PS1基因表达。[结果]1)与对照组相比,淫羊藿苷组、齐墩果酸组及补骨脂素组对APP基因下调均具有统计学意义(P<0.05)。2)与对照组相比,补骨脂素组有下调小鼠海马组织PS1基因的趋势,淫羊藿苷组及齐墩果酸组对PS1基因下调具有统计学意义(P<0.05)。[结论]补肾中药可能通过下调APP及PS1基因的表达,进而达到治疗老年性痴呆作用。     

左归降糖舒心方对糖尿病心肌病MKR鼠心肌细胞损伤和凋亡的影响＊

目的 观察左归降糖舒心方对糖尿病心肌病（Diabetic cardiomyopathy， DCM）模型鼠心肌细胞损伤和凋亡的影响，并探讨其作用机制。方法 以转基因2型糖尿病小鼠（MKR鼠）为实验对象，通过链脲菌素（streptozotocin， STZ）腹腔注射+持续高脂喂饲建立DCM模型，分为模型组、中药组、阳性药物组，另设C57小鼠为空白对照组。中药组给予左归降糖舒心方14.27 g生药/（kg·天）灌胃，阳性药物组给予二甲双胍250 mg/（kg·天）+依那普利4.5 mg/（kg·天）灌胃，连续给药4周。采用电化学法血糖仪测定空腹血糖（fasting blood glucose， FBG），光镜和透射电镜观察小鼠心肌组织形态学变化，ELISA法检测血清心肌肌钙蛋白I（cardiac troponin I， cTnI）、乳酸脱氢酶（lactic dehydrogenase， LDH）水平，免疫组化法检测I型胶原蛋白（Collagen-I）、III型胶原蛋白（Collagen-III）、Bcl-2相关X蛋白（Bcl-2 associated X protein， Bax）、半胱氨酸天冬氨酸蛋白酶-9（Caspase-9）、B淋巴细胞瘤-2基因（B-cell lymphoma-2， Bcl-2）的蛋白表达，TUNEL法检测心肌细胞凋亡。结果 模型组FBG较空白对照组显著升高，经左归降糖舒心方干预后明显降低（P<0.01）。与模型组比较，中药组和阳性药物组的心肌组织病理形态明显改善，Collagen-I、Collagen-III蛋白表达减弱（P<0.01），血清cTnI、LDH水平明显降低（P<0.01），细胞凋亡阳性表达减弱（P<0.01），Bax、Caspase-9表达减弱（P<0.01），Bcl-2表达增强（P<0.01）。中药组下调Collagen-I和Collagen-III表达、减少心肌细胞凋亡、下调Bax和Caspase-9表达等作用弱于阳性药物组（P<0.01），但上调Bcl-2表达的作用强于阳性药物组（P<0.01）。结论 左归降糖舒心方对糖尿病心肌病MKR鼠的心肌细胞损伤和凋亡具有保护作用，其作用机制可能与降糖、改善心肌纤维化、抑制促凋亡因子Bax和Caspase-9表达、促进抗凋亡因子Bcl-2表达等有关。     

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress,inflammation and apoptosis in rats

ObjectiveSalvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.MethodsIn a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5′-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.ResultsLiver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.ConclusionThis study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.     

The in-vivo assessment of Turkish propolis and its nano form on testicular damage induced by cisplatin

ObjectiveChemotherapeutic drugs, such as cisplatin (CP), which are associated with oxidative stress and apoptosis, may adversely affect the reproductive system. This study tests whether administration of propolis and nano-propolis (NP) can alleviate oxidative stress and apoptosis in rats with testicular damage induced by CP.MethodsIn this study, polymeric nanoparticles including propolis were synthesized with a green sonication method and characterized using Fourier transform-infrared spectroscopy, Brunauer-Emmett-Teller, and wet scanning transmission electron microscopy techniques. In total, 56 rats were divided into the following seven groups: control, CP, propolis, NP-10, CP + propolis, CP + NP-10, and CP + NP-30. Propolis (100 mg/kg), NP-10 (10 mg/kg), and NP-30 (30 mg/kg) treatments were administered by gavage daily for 21 d, and CP (3 mg/kg) was administered intraperitoneally in a single dose. After the experiment, oxidative stress parameters, namely, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), and apoptotic pathways including B cell leukemia/lymphoma-2 protein (Bcl-2) and Bcl-2-associated X protein (Bax) were measured in testicular tissues. Furthermore, sperm quality and weights of the testis, epididymis, right cauda epididymis, seminal vesicles and prostate were evaluated.ResultsPropolis and NP (especially NP-30) were able to preserve oxidative balance (decreased MDA levels and increased GSH, CAT, and GPx activities) and activate apoptotic pathways (decreased Bax and increased Bcl-2) in the testes of CP-treated rats. Sperm motility in the control, CP, and CP + NP-30 groups were 60%, 48.75%, and 78%, respectively (P < 0.001). Especially, NP-30 application completely corrected the deterioration in sperm features induced by CP.ConclusionThe results show that propolis and NP treatments mitigated the side effects of CP on spermatogenic activity, antioxidant situation, and apoptosis in rats.     

参芪复方对GK大鼠骨骼肌线粒体膜电位及相关促凋亡蛋白的影响研究＊

目的 探讨参芪复方对自发性糖尿病（Goto-Kakizaki，GK）大鼠骨骼肌线粒体膜电位及相关凋亡蛋白的影响。方法 采用高脂饲料喂养GK大鼠，建立糖尿病大鼠动物模型，造模成功后将GK大鼠随机分为模型组、罗格列酮组、参芪复方组，每组10只；10只Wistar大鼠作为空白对照组，普通饲料喂养。罗格列酮组灌胃给予0.67 mg/（kg·d）罗格列酮混悬液，参芪复方组灌胃给予14.33 g生药/（kg·d）参芪复方混悬液，空白对照组、模型组均每日灌胃给予同等体积生理盐水，连续给药8周。采用流式细胞检测线粒体膜电位；RT-qPCR和Western blot检测大鼠腓肠肌凋亡诱导因子（Aapoptosis inducing factor，AIF）、细胞色素C（Cytochrome c，Cyt c）、第二个线粒体衍生的半胱天冬蛋白酶激活因子（Second mitochondrial activator of caspase/direct IAP binding protein with low PI，Smac/DIABLO）、半胱氨酸天冬氨酸蛋白酶-9（Cysteinyl aspartate specific proteinase-9，Caspase-9）、半胱氨酸天冬氨酸蛋白酶-3（Cysteinyl aspartate specific proteinase-3，Caspase-3）的蛋白和mRNA表达情况。结果 与空白对照组比较，模型组GK大鼠腓肠肌线粒体膜电位降低（P < 0.05），AIF、Cyt c、Smac/DIABLO、Caspase-9、Caspase-3蛋白表达、mRNA表达增加（P < 0.05）；与模型组比较，罗格列酮组和参芪复方组线粒体膜电位均升高（P < 0.05），罗格列酮组AIF、Cyt c、Smac/DIABLO、Caspase-9、Caspase-3蛋白表达、mRNA表达均降低（P < 0.05），参芪复方组AIF、Cyt c、Caspase-9、Caspase-3蛋白表达、mRNA表达降低（P < 0.05），Smac/DIABLO 蛋白表达降低（P < 0.05），Smac/DIABLO mRNA表达具有下降趋势，但差异无统计学意义（P > 0.05）。结论 参芪复方可通过上调线粒体膜电位，抑制促凋亡蛋白AIF、Cyt c、Smac /DIABLO从线粒体内释放出来，进而抑制Caspase-9、Caspase-3表达，减少骨骼肌细胞凋亡，发挥骨骼肌保护作用。     

玉屏风水提液对环磷酰胺致大鼠骨质疏松骨形态计量学的影响

目的:观察环磷酰胺对大鼠骨形态计量学的影响,并探讨玉屏风水提液对环磷酰胺造成的骨质疏松的防治作用。方法:27只大鼠随机分为3组,正常对照组(Control):灌胃给予5mL/(kg.d)生理盐水。环磷酰胺组(CP组):灌胃给予环磷酰胺4.5mg/(kg.d)。玉屏风水提液组:灌胃给予环磷酰胺4.5mg/(kg.d)及玉屏风水提液(YPF组)5mL/(kg.d)。于实验第15d处死动物,取左侧胫骨进行骨组织形态计量动静态学参数骨小梁面积百分数(%,Tb.Ar),骨小梁厚度(Tb.Th),骨小梁数量(Tb.N),骨小梁分离度(Tb.SP),动态参数包括荧光标志周长百分数(%,L.Pm),矿化沉积率(MAR),骨小梁周长形成率(BFR/BS),骨小梁面积形成率(BFR/BV),骨小梁体积形成率(BFR/TV)测量。结果:环磷酰胺模型组骨形态计量动静态学参数较对照组下降(P<0.05或P<0.01),玉屏风水提液组骨形态计量动静态学参数与对照组比较无显著差异,较模型组有显著提高(P<0.05或P<0.01)。结论:环磷酰胺会引起大鼠骨形态计量学参数的变化,玉屏风水提液对此有防治作用。     

松针石油醚提取物抗肿瘤及诱导凋亡作用

目的:探讨松针石油醚提取物抗肿瘤作用机制。方法:建立荷S 180实体瘤小鼠模型,考察松针石油醚提取物体内抗肿瘤作用。应用免疫组化法检测肿瘤组织中凋亡相关蛋白Bax,Bcl-2的表达。结果:松针石油醚提取物0.5,1.0,2.0 g.(kg.d)-1 3个剂量组对S 180实体瘤的抑瘤率分别为31.16%,41.71%,42.16%。各用药组肿瘤组织Bax表达显著增强,Bcl-2表达显著降低。结论:松针石油醚提取物具有一定的抗肿瘤活性,诱导凋亡是其机制之一。     

补肾益气方药对心衰大鼠胰岛素抵抗及PKB、脂联素蛋白表达的影响＊

目的 探讨补肾益气方药对充血性心力衰竭大鼠胰岛素抵抗及PKB、脂联素蛋白表达的影响。方法 选用健康雄性Wistar大鼠60只，对照组10只，其余50只均用阿霉素腹腔注射，建立充血性心力衰竭大鼠模型。造模成功后将Wistar雄性大鼠随机分为模型组、卡托普利组（25 mg/kg·d）、补肾益气方药低剂量组（4 g/kg·d）、中剂量组（6 g/kg·d）、高剂量组（8 g/kg·d）。葡萄糖氧化酶法测定空腹血糖（Fasting Blood-Glucose, FBG）；放射性免疫法测定空腹胰岛素（Fasting inshulin, FIS），计算胰岛素敏感性指数（Insulin Sensitivity Index，ISI）；Western Blot 技术检测PKB、脂联素蛋白表达，RT-PCR 方法检测PKB、脂联素的mRNA表达。结果 与空白对照组相比，模型组FBG、FIS显著增加（P < 0.01），ISI显著降低（P < 0.01）；与模型组比较，补肾益气方药高剂量组FBG显著降低（P < 0.05），卡托普利组及补肾益气方药各剂量组FIS明显降低（P < 0.05），卡托普利组及补肾益气方药中高剂量组ISI显著升高（P < 0.05）。与空白对照组相比，模型组心脏、肝脏与骨骼肌组织PKB、脂联素mRNA与蛋白表达均显著下降（P < 0.01）；与模型组比较，卡托普利组及补肾益气方药各组可呈剂量依赖性显著增加PKB、脂联素mRNA与蛋白表达（P < 0.05）。结论 补肾益气方药可能通过增加PKB、脂联素基因转录与及其蛋白表达，改善充血性心衰大鼠胰岛素抵抗，保护心肌细胞，改善心功能。     

甘草地上部分的安全性评价

目的:评价甘草地上部分的毒理学安全性,为合理利用甘草地上部分资源提供依据。方法:采用急性经口毒性实验、小鼠骨髓细胞微核实验、小鼠精子畸形实验以及基于炎症模型的安全性实验的方法,并对实验结果进行统计分析与判定。结果:甘草地上部分水提物和醇提物对小鼠的最大耐受剂量(MTD)分别为96,128 g·kg~(-1),醇提物大孔树脂富集产物对小鼠有伤害且表现出性别差异。骨髓细胞微核实验甘草地上部分水提物低、中、高剂量(8,16,32 g·kg~(-1))组和正常组的微核率分别为0. 28%,0. 34%,0. 26%,0. 22%(雌性)和0. 32%,0. 30%,0. 36%,0. 28%(雄性);小鼠精子畸形实验甘草地上部分低、中、高剂量(8,16,32 g·kg~(-1))组和正常组的精子畸形率分别为3. 16%,3. 01%,2. 67%,3. 23%;微核率和精子畸形率与正常组比较无明显增加; 30 d重复灌胃水提物和醇提物对模型大鼠的一般情况无影响,其中,与正常组比较,甘草地上部分醇提组心脏质量显著降低(P 0. 05),肝脏质量、肝脏指数和肾脏指数明显升高(P 0. 05);水提组与醇提组的球蛋白与血肌酐明显升高(P 0. 05),个别大鼠氨基转移酶异常;解剖学考察发现4例肉眼可见的肝病变,其中甘草地上部分水提组3例,甘草地上部分醇提组1例,组织病理学检查发现肝细胞变性与组织炎症,与出现生化指标与脏器指数异常的大鼠一致。结论:甘草地上部分水提物、醇提物具有潜在毒性,水提物未显示对小鼠有遗传毒性,其安全性尚需进一步研究。     

阿魏酸钠和白芍总苷对小鼠H22肿瘤生长与血管内皮细胞生长因子及增殖细胞核抗原表达的影响

目的探讨阿魏酸钠及白芍总苷对小鼠H22肿瘤生长及血管生成的影响。方法昆明小鼠前腋下皮下接种小鼠H22肝癌细胞,第2天ip阿魏酸钠(200、100、50mg/kg)或ig白芍总苷(200、100、50mg/kg),每3天测量1次肿瘤体积。用免疫组化法标记肿瘤血管及测定血管内皮细胞生长因子(VEGF)及增殖细胞核抗原(PCNA)的表达。MTT法检测阿魏酸钠对H22肿瘤细胞体外增殖的影响。结果阿魏酸钠组小鼠H22肿瘤体积、质量增长明显较模型组缓慢(P<0.05),同时阿魏酸钠组的肿瘤微血管密度及VEGF、PCNA阳性细胞较模型组显著减少(P<0.05),阿魏酸钠对小鼠H22肿瘤细胞体外增殖无显著抑制作用。白芍总苷各剂量组的肿瘤生长、微血管密度、H22肿瘤细胞增殖与模型组相比均无显著性差异。结论阿魏酸钠可以显著抑制小鼠H22肿瘤的生长及血管生成,且能抑制VEGF的表达。但在体外实验中不能抑制H22肿瘤细胞的增殖。白芍总苷尚不能被证明有抑制小鼠H22肿瘤生长的作用。阿魏酸钠对肿瘤组织VEGF表达的抑制作用可能是其抗H22肿瘤及抗血管生成的一个重要原因。     

Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira)

Ethnopharmacological relevance

Bowdichia virgilioides Kunth (Leguminosae Papilonoideae) is a plant with anti-inflammatory activity used in folk medicine. The importance of this plant promoted its inclusion in Brazilian Pharmacopoeia.

Aim of the study

In order to evaluate the actions of this plant, studies were performed on antinociceptive and anti-inflammatory activities.

Materials and methods

The aqueous extracts (AE) of Bowdichia virgilioides inner bark and leaves were used at 100, 200, and 400 mg/kg. Antinociceptive activity of plant extract was evaluated by writhing, hot-plate and formalin tests. Anti-inflammatory activity was evaluated using paw oedema and peritonitis methods.

Results

Oral treatment with the AE of inner bark or leaves elicited inhibitory activity (P < 0.01) on acetic acid effect at 200 and 400 mg/kg, and reduced the formalin effect at the second-phase (200 and 400 mg/kg, P < 0.01), however it did not elicit any inhibitory effect on hot-plate test. The indomethacin inhibited the acetic acid-induced writhing and the formalin effect at the second-phase (P < 0.001), and the morphine reduced the both phases of formalin test (P < 0.001). Carrageenan-induced oedema formation and neutrophil migration into the peritoneal cavity were reduced with the AE of inner bark or leaves at 100, 200, and 400 mg/kg (P < 0.05), and by the reference compounds aspirin (P < 0.001) and dexamethasone (P < 0.001), respectively.

Conclusions

The AE of Bowdichia virgilioides shows antinociceptive and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.     

Protective Effects of Total Flavonoids from Epimedium on the Male Mouse Reproductive System Against Cyclophosphamide‐Induced Oxidative Injury by Up‐Regulating the Expressions of SOD3 and GPX1

Total flavonoids of Epimedium (TFE) is the main active composition of Epimedium that has been used to treat male reproductive problems. The present aim was to investigate the protective effects of TFE on male mice reproductive system against cyclophosphamide (CP)‐induced oxidative injury. The animals were treated with CP to make testicular injury model and the protective effects of TFE were observed. In the CP‐treated group, testicular and epididymal weights, sperm count and motility significantly decreased relative to the control group (P < 0.05 and P < 0.01, respectively). Compared with the CP‐treated group, TFE (200 and 400 mg/kg) treated mice increased testicular weights by 21.6% and 28.4% (P < 0.05), sperm counts by 81.7% and 148.3% (P < 0.01) and sperm motility by 47.2% and 61.3% (P < 0.01). Meanwhile, the CP‐treated group showed enhancement of lipid peroxidation leading to testicular reproductive toxicity. TFE restored these oxidative damages by up‐regulating the expression of antioxidant enzymes, especially SOD3 and GPX1. TUNEL assay and histopathological observations provided supportive evidence for above results, and when the dose of TFE increased, the aforesaid improvement became more and more strong. These results demonstrated that TFE exerted beneficially protective effects on the structural and functional damage of male mice reproductive system and reduced apoptosis in spermatogenic cells by inhibiting CP‐induced oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.     

铁调素高表达与内皮损伤的相关性及川芎嗪的干预作用

目的探讨血管内皮损伤与铁调素(hepcidin)高表达的相关性,以及川芎嗪对其的干预作用。方法 24只SD大鼠随机分为4组:对照组、模型组、肝素阳性对照组(肝素组)及川芎嗪组,每组6只。对照组大鼠以普通饲料喂养,其余3组以高脂饲料喂养。8周后,对照组及模型组大鼠ip给予生理盐水2mL/kg,肝素组ip给予肝素钠注射液5mg/kg,川芎嗪组ip给予盐酸川芎嗪注射液40mg/kg,均连续给药7d。大鼠腹主动脉取血后分离血清,检测各组大鼠血脂指标,检测血清铁调素、一氧化氮(NO)、内皮素1(ET-1)、活性氧(ROS)、丙二醛(MDA)、过氧化氢酶(CAT)及超氧化物歧化酶(SOD)水平;截取主动脉组织,进行铁含量检测及组织病理学观察。结果与对照组比较,模型组大鼠血清铁调素、ET-1、ROS、MDA水平均升高(P0.05、0.01),而NO、SOD及CAT水平均降低(P0.05、0.01);主动脉内铁含量明显升高(P0.01),且主动脉组织出现了内膜损伤。与模型组比较,肝素组和川芎嗪组大鼠血清铁调素、ET-1、ROS、MDA水平均显著降低(P0.05、0.01),NO及CAT水平均显著升高(P0.01),SOD水平有升高趋势;主动脉组织内铁含量均降低(P0.05、0.01),且主动脉组织内膜损伤有所减轻。结论内皮损伤程度加重的同时铁调素呈高表达状态,应用川芎嗪后,内皮损伤减轻,铁调素水平下降,说明川芎嗪对内皮的保护作用可能与其对铁调素高表达的抑制有关。     

补肾益智方对老年性痴呆模型动物空间探索学习记忆功能的改善作用

目的观察补肾益智方对老年性痴呆(AD)模型大鼠空间探索学习记忆功能的改善作用.方法用15月龄老年Wistar大鼠80只,以D-半乳糖ip4周加上鹅膏蕈酸(ibotenic acid,IBO)脑内Meynert核注射制造AD模型,随机分成AD模型组,双益平治疗对照组,补肾益智方高、低剂量(12,6 g/kg@d)治疗组.另加上正常老年组和正常青年组总共设立6个组别.动物经治疗处理4周后,应用Morris水迷宫检测大鼠学习记忆的改善情况.结果空间探索试验发现,模型组及双益平组在空间探索试验中的指标与正常青年组和正常老年组有显著差异性(P＜0.01或P＜0.05);补肾益智方高、低剂量组也与模型组和双益平组有显著性差异(P＜0.01或P＜0.05).与模型组比较,正常青年组、正常老年组和补肾益智方高剂量组第7天撤离平台后大鼠在原平台象限内游泳的时间占整个游泳时间的百分比明显要高(P＜0.05),而补肾益智方低剂量和双益平组虽然要高些,但差异无显著性(P＞0.05).结论补肾益智方能明显改善AD大鼠空间探索学习记忆功能.     

丹皮酚和芍药苷配伍对大鼠心肌缺血损伤的保护作用

目的:研究丹皮酚和芍药苷配伍对实验性心肌缺血大鼠心肌损伤的保护作用.方法:采用在体结扎大鼠心脏冠状动脉前降支法建立大鼠心肌缺血损伤模型.实验分为假手术组、模型组、阳性药对照组(复方丹参片840 mg·kg-1)、丹芍配伍高剂量组(丹皮酚100 mg·kg-1+芍药苷25 mg·kg-1)、丹芍配伍中剂量组(丹皮酚50 mg·kg-1+芍药苷12.5 mg·kg-1)、丹芍配伍低剂量组(丹皮酚25 mg·kg-1+芍药苷6.25 mg· kg -).ig给药容积10 mL·kg-1,连续给药5d,1次/d,假手术组和模型组ig等量生理盐水.观测大鼠心电图(ECG),测定大鼠血清天门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)的活性,硝基四氮唑蓝(N-BT)染色测定心肌梗死面积.结果:与梗死模型组比较,丹芍配伍高、中剂量组均可明显减轻冠脉结扎形成的大鼠急性心肌缺血性心电图的(ST段抬高及T波高耸)变化程度(P＜0.05),缩小心肌梗死面积(P＜0.05或P＜0.01),同时能够降低血清中AST、CK、LDH的升高程度(P＜0.05或P＜0.01).结论:丹芍配伍对大鼠急性心肌缺血损伤具有明显保护作用.     

丹酚酸B对糖尿病动脉粥样硬化斑块内血栓相关因子的影响

[目的]观察丹酚酸B对抗糖尿病动脉粥样硬化斑块血栓形成的作用及可能的发生机制。[方法]选取50只8周龄雌性ApoE-/-小鼠,腹腔注射链尿佐菌素200 mg/kg联合高脂饲料喂养12周,将血糖水平11.1 mol/L 40只ApoE-/-小鼠作为糖尿病动脉粥样硬化模型小鼠,随机分为模型组(MOD)、丹酚酸B高剂量组(SalBH)、丹酚酸B中剂量组(SalBM)与洛伐他汀组(LVT)4组,每组10只。各组均连续灌胃8周。实验期满后,测定空腹血糖水平;酶联免疫吸附(ELISA)法检测血清I型纤溶酶原激活物抑制剂(PAI-1)的浓度。免疫组织化学染色检测斑块内组织因子(TF)的表达,利用Image-Pro Plus Version 6.0(IPP)图像分析系统计算结果。[结果]与MOD组比较,各治疗组TF平均光密度值明显降低(P0.05);与MOD组比较,SalBM组PAI-1浓度明显降低(P0.05)[。结论]丹酚酸B能够降低糖尿病动脉粥样硬化斑块内TF的表达和血清PAI-1含量,提示丹酚酸B可能是通过以上机制来减少粥样硬化斑块内的血栓形成。     

Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver

ObjectiveATP-binding cassette transporter A1 (ABCA1) is an integral membrane protein that plays a key role in cellular lipid metabolism, preventing the accumulation of lipids that contribute to the initiation and progression of atherosclerosis. Tiaozhi Tongmai Granules are a Chinese herbal compound that is capable of treating atherosclerosis. This study was designed to explore the potential pharmacological mechanism by which Tiaozhi Tongmai Granules protect against atherosclerosis.MethodsForty-nine male New Zealand rabbits were randomly divided into seven groups: normal control group, normal diet; model groups 1 and 2: balloon injury and high-fat diet for 6 or 12 weeks; statin groups 1 and 2: balloon injury and high-fat diet plus atorvastatin for 6 or 12 weeks; and Chinese herb groups 1 and 2: balloon injury and high-fat diet plus Tiaozhi Tongmai Granules for 6 or12 weeks. The granules were administered at a dose of 1.14 g/kg/d, with atorvastatin (1.14 mg/kg/d) serving as positive control. Serum lipid profiles and liver function indices were measured. Atherogenesis was viewed after H&E staining and quantified by thickened intimal area percentage and maximal intimal thickness percentage. The ABCA1 protein expression in atherosclerotic plaque macrophages of the common carotid arteries (CCA), thoracic aortae (TA), and liver tissues were observed by immunohistochemical staining and evaluated using mean optical density (OD) value in macrophages and ABCA1-positive hepatocyte number.ResultsCompared with model group 1 at week 6, Chinese herb group 1 and statin group 1 displayed significant reductions in total cholesterol (TC) (P = 0.027, 0.012) and low-density lipoprotein cholesterol (LDL-C) (P = 0.039, 0.028) levels, as well as marked increases in ABCA1-positive hepatocyte numbers (P all <0.001), and only statin group 1 displayed a markedly reduced maximal intimal thickness percentage in the CCA (P = 0.018). Compared with model group 2 at week 12, Chinese herb group 2 and statin group 2 all presented significant reductions in TC (P = 0.011, 0.003), LDL-C (P = 0.017, 0.010) and thickened intimal area percentage in the CCA (P = 0.001, 0.022), as well as prominent increases in the ABCA1 OD value of both the CCA (P = 0.001, 0.039) and TA (P = 0.001, 0.025) and positive hepatocyte number (P all <0.001). Chinese herb group 2 had a markedly reduced maximal intimal thickness percentage compared with model group 2 (P = 0.006) and a higher positive hepatocytes number than statin group 2 (P = 0.001).ConclusionsTiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit atherosclerotic plaque macrophages and in the liver.     

Moxibustion pretreatment inhibits RhoA/ROCK signaling to prevent lung inflammation in asthmatic rats: 艾灸预处理降低RhoA/ROCK信号表达预防哮喘大鼠肺炎

Objective: To determine whether pretreatment moxibustion prevents asthma by down-regulating the lung RhoA/ROCK pathway in rats with bronchial asthma and benignly mediating the lung inflammatory response.Methods: Twenty Sprague Dawley (SD) rats were randomly divided into normal control group (C), asthma model group (M), suspended moxibustion 40 min +asthma group (SM40), and suspended moxibustion 10 min +asthma group (SM10). Ovalbumin was used as a sensitizer. The two moxibustion groups completed moxibustion treatment lasted 40 min or 10 min respectively 30 min before modeling onset, and was repeated five times in each modeling cycle, for a total of 15 times. Samples were harvested on day 30.Results: Lung impairment was significant in the M group, whereas pretreatment with SM10 and SM40 dramatically attenuated the injury. After modeling, mRNA expression of RhoA and ROCK2 in the lung tissue was significantly higher than that in C group (both P < 0.001), resulting in significant increase in protein levels of IL-17A (P < 0.001). Significant decrease in RhoA and ROCK2 mRNA expression was seen in the SM10 (P<0.001, P<0.01) and SM40 (both P<0.001) groups compared to that with M rats. The differential trend in the SM40 group was more evident than that in the SM10 group. Regarding IL-10 or IL-17A protein concentration, an upregulation or down-regulation was observed in both SM10 (P<0.05, P < 0.01) and SM40 groups (both P < 0.001) compared to that with the M group.Conclusions: Moxibustion pretreatment significantly prevented pulmonary inflammation in asthmatic rats, potentially via inhibition of the RhoA/ROCK pathway. The efficacty of moxibustion appeared to be significantly associated with the duration of intervention with moxibustion.