表没食子儿茶素没食子酸酯改善高脂饮食大鼠体重及相关代谢研究

目的:观察不同剂量表没食子儿茶素没食子酸酯(EGCG)对高脂饮食大鼠体重、糖脂代谢及肝脏氧化应激状态的影响,为深入研究EGCG防治肥胖的机制探索最佳干预剂量。方法:40只雄性SD大鼠随机分为正常对照组、高脂饮食组、EGCG低剂量组[100 mg/(kg·d)]、EGCG中剂量组[200 mg/(kg·d)]、EGCG高剂量组[400 mg/(kg·d)],每组8只。正常对照组喂饲基础饲料,高脂饮食组喂饲高脂饲料,EGCG各组喂饲高脂饲料的同时给予各剂量EGCG灌胃。喂养8周末处死大鼠。测定体重、内脏脂肪重量、肝脏重量、血清空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、肝脏总超氧化物歧化酶(T-SOD)活性、谷胱甘肽过氧化物酶(GPx)活性、丙二醛(MDA)含量。结果:高脂饮食组实验末体重、肝脏重量、血清FBG均显著高于正常对照组(P<0.05)。与高脂饮食组相比,EGCG各剂量组能有效降低高脂饮食大鼠体重、肝脏重量、血清FBG和TG水平(均P0.05)。与高脂饮食组相比,低剂量EGCG可升高肝脏GPx活力(P<0.05)。中剂量EGCG可降低肝脏MDA含量(P0.05)。结论:中剂量EGCG对控制高脂饮食大鼠体重、改善糖脂代谢及肝脏氧化应激状态更为适宜,而高剂量EGCG可能反而会促进机体氧化应激水平。     

北五味子多糖对高脂血症大鼠肝损伤的影响

目的探讨北五味子多糖(SCP)对高脂饮食诱导肝损伤大鼠肝功能的保护作用。方法采用高脂饲料喂养16 w诱发高脂血症大鼠模型,随机分为模型组及SCP治疗组,另设正常对照组以及正常+SCP组。SCP(50 mg/kg)灌胃给药12 w,检测各组动物血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,肝组织中TG和TC水平;苏木素-伊红(HE)染色观察药物对肝组织病理学改变的影响。结果与正常对照组比较,模型组大鼠血清中TC、TG、LDL-C、ALT及AST水平显著增高(P<0.01),肝组织中TG和TC水平显著增高(P<0.01)。与模型组比较,SCP显著降低了大鼠血清TC、TG、LDL-C水平(P<0.05或P<0.01)、ALT、AST水平(P<0.01),降低肝组织中TG和TC水平(P<0.01),而对正常大鼠血脂、肝脂质和肝功能没有明显影响。HE染色显示模型组大鼠肝小叶结构紊乱,出现明显的肝细胞脂肪变性;SCP组肝小叶结构基本正常,肝脏脂肪变性明显减轻。结论 SCP可改善高脂血症大鼠脂质代谢紊乱,改善肝功能,减轻肝损伤。     

超微脂康饮对非酒精性脂肪性肝病大鼠模型的疗效

目的观察超微脂康饮对实验性非酒精性脂肪肝(NAFLD)大鼠模型的疗效。方法 SD大鼠高脂饮食饲养6周后诱导非酒精性脂肪肝大鼠模型,肝脏病理切片证实造模成功;造模大鼠50只随机分为5组,超微脂康饮(低、中、高剂量)组给予相应剂量的超微脂康饮灌胃,壳脂胶囊组给予壳脂胶囊混悬液,模型组及空白组灌服蒸馏水,除空白组外,其余组仍予高脂饮食。6周后分别检测各组的肝功能、血脂、肝脂及肝脏组织学改变。各组之间比较采用单因素方差分析。结果超微脂康饮各组血清ALT、AST、肝组织脂质(TC、TG)等方面均优于模型组,差异均有统计学意义(P值均0.05),超微脂康饮中,低剂量组血清TG、TC显著优于模型组,差异均有统计学意义(P值均0.05);超微脂康饮各组血清ALT、AST、肝组织TC与壳脂胶囊组比差差异无统计学意义(P值均0.05)。模型组及超微脂康饮各组均存在不同程度的肝脏炎症活动度,但与模型组比较,超微脂康饮各组、壳脂胶囊组大鼠的肝脏炎症活动度均有不同程度的改善(P值均0.05),而壳脂胶囊组较超微脂康饮各组改善稍明显(P值均0.05)。结论超微脂康饮能改善NAFLD大鼠肝功能、降低血脂、抑制肝脏炎症,整体疗效与壳脂胶囊相当,对非酒精性脂肪肝具有一定疗效。     

祛湿化瘀方防治实验性脂肪肝的药效学研究

目的:探讨中药祛湿化瘀方防治脂肪肝的作用.方法:采用Wistar 雄性大鼠,以四氯化碳(CCl4)皮下注射复合高脂低蛋白饮食制备大鼠脂肪肝模型.在造模2周后,将造模大鼠随机分为模型组、祛湿化瘀方高剂量组、中剂量组和低剂量组,灌胃用药2周.观察大鼠体重、肝指数、血清丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)活性、肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量以及肝组织病理变化(HE染色).结果:模型组肝组织出现明显大泡样脂肪变性;肝组织TG、FFA含量以及血清ALT、AST、GGT活性显著升高.祛湿化瘀方各剂量组的病理改变较模型组显著减轻;肝组织 TG、FFA含量和血清ALT、AST、GGT活性显著低于模型组.其中高剂量组降低ALT的作用显著强于中、低剂量组.结论:祛湿化瘀方防治实验性脂肪肝疗效显著.     

脂肪肝1号方治疗非酒精性脂肪性肝炎的实验研究

目的:研究脂肪肝1号方治疗非酒精性脂肪性肝炎(NASH)的作用。方法:将48只SPF级SD雄性大鼠随机分为正常组,模型组,脂肪肝1号方高、中、低剂量组和易善复组,每组8只。采用高脂饲料喂养造模,共8周,药物灌胃与造模同时进行。脂肪肝1号方高、中、低剂量组大鼠分别以生药含量为10.8g/(kg·d)~(-1)、5.4g/(kg·d)~(-1)、2.7g/(kg·d)~(-1)脂肪肝1号方中药煎剂灌胃;易善复组以0.123g/(kg·d)~(-1)易善复混悬液灌胃。分别于第0周、第2周、第4周、第6周、第8周末称量大鼠体质量,第8周末处死大鼠,检测大鼠血清肝酶(ALT、AST)、血脂(TG、TC)水平;肝组织石蜡切片行HE染色、冰冻切片行油红O染色,观察肝脏病理学特征,并进行NAS评分。结果:①大鼠体质量变化:第0、2周,各组大鼠体质量差异未见统计学意义(P0.05);第4周末,脂肪肝1号方高剂量组大鼠体质量与模型组相比显著降低(P0.01);第6周末,脂肪肝1号方高、中剂量组和易善复组大鼠体质量与模型组相比均显著降低(P0.05或0.01),且脂肪肝1号方高剂量组大鼠体质量显著低于中剂量组和易善复组;第8周末,脂肪肝1号方高、中、低剂量组和易善复组大鼠体质量与模型组相比均显著降低(P0.05或0.01),且脂肪肝1号方高剂量组大鼠体质量显著低于中、低剂量组和易善复组(P0.01)。②肝酶和血脂的变化:与模型组相比,脂肪肝1号方高、中剂量组和易善复组大鼠血清肝酶、血脂水平均显著下降(P0.05或0.01),且脂肪肝1号方高剂量组大鼠肝酶水平显著低于中剂量组、低剂量组、易善复组3组大鼠(P0.01),但脂肪肝1号方高、中剂量组及易善复组大鼠血脂水平未见明显差异(P0.05)。③肝脏病理变化:与模型组相比,肝脂肪性病变、小叶内炎症、气球样变、肝组织脂滴沉积状况在脂肪肝1号方高、中剂量组和易善复组中均得到明显改善,且NAS评分具有显著性差异(P0.01)。结论:脂肪肝1号方可有效减轻高脂饲料所致的NASH大鼠体质量,降低大鼠肝酶、血脂水平,改善肝组织脂肪性病变。     

普罗布考和阿托伐他汀联合用药对高脂饮食自发性高血压大鼠肝脏的影响

目的 对普罗布考和阿托伐他汀联合用药对肝脏的安全性进行评价.方法 将92只雄性自发性高血压大鼠随机分为5组,对照组:普通饲料+生理盐水;高脂组:高脂饲料+生理盐水;普罗布考组:高脂饲料+普罗布考150 mg/(kg·d);阿托伐他汀组:高脂饲料+阿托伐他汀10 mg/(kg·d);联合用药组:高脂饲料+阿托伐他汀10 mg/(kg·d)+普罗布考150 mg/(kg·d),实验8周后处死.实验结束时抽血测血脂、高敏C-反应蛋白和肝功能,留肝脏标本行病理切片观察其脂肪变性及炎症程度.结果 ①高脂饮食各组总胆固醇和低密度脂蛋白胆固醇均高于对照组(P<0.01),而二药合用组较普罗布考组、阿托伐他汀组明显降低(P<0.05);②高脂组血清高敏C-反应蛋白、丙氨酸氨基转移酶和天门冬氨酸氨基转移酶水平较对照组明显升高(P<0.01),二药合用组明显低于高脂组和阿托伐他汀组(P<0.01);③高脂饮食各组均发生肝脏脂肪变性,高脂组最重,二药合用组较普罗布考组和阿托伐他汀组明显减轻(P<0.05);④肝脏炎性活动度评分二药合用组明显低于高脂组、阿托伐他汀组(P<0.01).结论 ①高脂饮食可引起血脂、炎症因子的紊乱,并可导致肝功能的损害和肝细胞脂肪变性及坏死;②普罗布考联合阿托伐他汀可减轻血脂和炎症因子的紊乱以及肝脏的脂肪变性和坏死程度,较二者单独用药效果更好;③二者联合用药可明显减轻高脂饮食引起的肝功能损害,且可减轻阿托伐他汀的肝毒性.     

罗格列酮对高脂饮食诱导非酒精性脂肪肝大鼠胰岛素抵抗及脂联素的影响

目的:探讨罗格列酮对高脂饮食所致的非酒精性脂肪肝大鼠模型胰岛素抵抗及脂联素的影响.方法:30只大鼠随机分为3组,即模型组(高脂饮食 蒸馏水ig),空白对照组(正常饲料 蒸馏水ig)和罗格列酮组[高脂饮食 罗格列酮3 mg/(kg·d)ig].观察各组血脂、肝功、胰岛素抵抗指数(HOMA-IR)的变化和各组肝组织HE染色与脂肪特异性的苏丹Ⅲ染色的变化.采用实时荧光定量聚合酶链式反应(PCR)和免疫印迹(western blot)检测各组肝组织的脂联素水平.结果:模型组与空白对照组相比,甘油三酯(TG)(1.51±0.37 mmol/L vs 0.98±0.51 mmol/L,P<0.01),总胆固醇(TC)(2.74±0.65 mmol/L vs 1.71±0.37 mmol/L,P<0.05),ALT(450.20±244.12 U/L vs 264.56±48.44 U/L,P<0.011,AST(460.30±310.13 U/L vs 196.11±52.23 U/L,P<0.01)和HOMA-IR(3.46±1.16 vs 1.07±0.26,P<0.01)均显著升高.罗格列酮治疗可使TG(1.27±0.50 mmol/L),ALT(360.26±244.37 U/L,AST(300.20±233.13 U/L)以及HOMR- IR(1.44±0.37)得到明显改善(均P<0.05).从组织病理学亦可得到证实.肝组织实时荧光定量PCR及免疫印迹显示罗格列酮组的Adiponectin mRNA(552.40±268.13 vs 215.95±135.87,P<0.05)和蛋白表达均较模型组升高.结论:高脂饮食可诱导大鼠NAFLD和IR发生,并使肝功,血脂异常升高.罗格列酮可以改善高脂饮食大鼠的脂肪肝及IR情况,可能与Adiponectin缓解IR和NAFLD改善有关.     

褪黑素对糖尿病大鼠心功能及氧化应激反应的影响

目的 探讨褪黑素(MT)对糖尿病大鼠心脏功能及心肌组织中丙二醛(MDA)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)含量的影响.方法 雄性Wistar清洁级大鼠,高脂高糖饮食配合腹腔注射链脲佐菌素诱导糖尿病模型,直接给予低剂量〔10 mg/(kg体重·d)〕和高剂量〔20 mg/(kg体重·d)〕MT灌胃...     

虎杖降脂颗粒对高脂血症大鼠降脂作用的研究

目的研究虎杖降脂颗粒对饮食性大鼠高脂血症的治疗作用。方法采用高脂性饮食诱导大鼠高脂血症,给予口服不同剂量的虎杖降脂颗粒,观察药物对模型动物血脂水平、体质量变化和肝脏脏器指数,肝脏脂质TC、TG,血清AST、ALT、肌酐和尿素氮以及肝脏组织形态的影响。结果虎杖降脂颗粒各剂量组大鼠肝指数及肝组织脂质TC和TG均明显下降(P0.05或P0.01);血清中TC、LDL-C、HDL-C含量不同程度地降低(P0.05或P0.01),但对TG作用不明显;血清AST、ALT有不同程度的降低(P0.05或P0.01),但对血清肌酐和尿素氮无明显作用。肝组织病理学结果表明,虎杖降脂颗粒各剂量组能不同程度地降低模型大鼠的肝脏脂肪变性程度。结论虎杖降脂颗粒可有效调节高脂乳剂所致高脂血症大鼠血脂和肝脂水平,对高脂血症具有较好的调脂作用。     

赶黄草对大鼠酒精性脂肪肝的保护作用及机制

目的探讨赶黄草对大鼠酒精性脂肪肝的保护作用及机制。方法随机选择140例大鼠,喂以1.5%的硫酸亚铁饲料进行饲养,并进行灌胃乙醇制作酒精性脂肪肝大鼠模型。将所有大鼠随机分为正常对照组、模型组、赶黄草提取物高剂量、低剂量组、槲皮素高剂量、低剂量组、硫普罗宁组共七组,用药大鼠均灌胃给药,1次/d,连用6 w。计算肝脏系数,并行肝组织油红O染色,于光镜下观察肝脏脂肪浸润情况,对比肝细胞脂滴面积,并检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清总胆固醇(TC)及甘油三酯(TG)含量。结果 1相比正常对照组,模型组大鼠反应迟钝,体重明显减轻,肝脏指数明显增加(P0.05);相比模型组,各用药组大鼠体重增加显著,肝脏指数明显下降(P0.05)。2油红O染色脂滴半定量分析后显示,赶黄草提取物各剂量组同模型组比较均有明显差异(P0.05)。3相比正常对照组,模型组血清ALT、AST、TC、TG水平均增加(P0.05);相比模型组,各用药组血清ALT、AST、TC、TG水平均降低(P0.05);相比槲皮素各组,赶黄草各提取物组ALT、AST、TC、TG水平均降低(P0.05)。结论赶黄草对大鼠酒精性脂肪肝有明显保护作用,与其中含有的槲皮素及其他化学成分有关。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.