荷丹片干预非酒精性脂肪性肝炎大鼠的疗效观察

目的:观察荷丹片对非酒精性脂肪性肝炎(NASH)大鼠的干预作用。方法:雄性SD大鼠40只,随机分为4组:正常组、模型组、阳性对照组和荷丹片治疗组。除正常组外,其余各组大鼠给予高脂饲料喂养,造模8周后开始药物灌胃干预,治疗4周后处死全部动物,应用全自动生化分析仪、放免法等进行血清生化和肝组织生化指标检测,并在HE染色光镜下观察大鼠肝组织病理形态学改变。结果:与模型组相比,荷丹片治疗后可明显降减低大鼠血清及肝组织中胰岛素抵抗相关指标:血糖(Glu)、胰岛素(INS)及游离脂肪酸(NEFA)水平,增加肝组织中超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)含量。光镜观察发现荷丹片能明显缓解NASH大鼠肝细胞脂肪变性,减轻肝小叶中炎性细胞浸润。结论:荷丹片能够通过缓解胰岛素抵抗、调节抗氧化功能等途径降低NASH大鼠肝细胞中的脂质蓄积,从而改善肝功能。     

肾气丸对非酒精性脂肪性肝炎大鼠肝细胞脂性凋亡的影响

[目的]探讨肾气丸对高脂饮食诱导的非酒精性脂肪性肝炎（NASH）大鼠肝细胞脂性凋亡的影响。[方法]采用高脂饲料连续喂养12周建立大鼠NASH模型,40只大鼠随机分为4组,正常组予以标准饲料喂养,其余3组进行高脂饮食造模,除模型组外,其他2组分别以肾气丸、二甲双胍进行干预12周。全自动生化仪检测血脂及血清酶学,ELISA法检测血清游离脂肪酸（FFA）水平;苏木精-伊红染色光镜下观察肝组织病理学变化,计算非酒精性脂肪性肝病（NAFLD）炎症活动度积分（NAS）;TUNEL法检测肝细胞凋亡水平,计算凋亡指数（AI）。[结果]NASH模型组大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、FFA水平均较正常组明显增高（P〈0.05,〈0.01）,血清三酰甘油（TG）水平较正常组明显降低（P〈0.05）,肝组织NAS、AI明显高于正常组（P〈0.01）。应用肾气丸和二甲双胍干预后,血清ALT、AST、TC、LDL-C、FFA水平均较模型组明显降低（P〈0.05）,血中TG、高密度脂蛋白胆固醇（HDL-C）与模型组比较差异无统计学意义（P〉0.05）。肝组织NAS和AI较模型组显著降低。相关性分析发现,大鼠肝细胞的AI与肝组织NAS及血清FFA水平呈明显正相关（均P〈0.01）。[结论]NASH大鼠存在着脂质代谢紊乱和肝细胞的脂性凋亡。肾气丸与二甲双胍作用相似,可能是通过调节脂质代谢,影响FFA,阻断其引发的促肝细胞脂性凋亡的级联启动,从而有效地防治NASH的进展。     

ω-3多不饱和脂肪酸防治非酒精性脂肪性肝炎大鼠的初步观察

目的观察多不饱和脂肪酸对非酒精性脂肪性肝炎（NASH）大鼠糖脂代谢、肝脏脂质沉积及血清脂肪细胞因子的影响。方法随机将32只大鼠分成3组,正常组给予普通饲料喂养,模型组和治疗组给予高脂饲料喂养制备NASH模型。治疗组在喂养8周后加用ω-3多不饱和脂肪酸干预,12周后处死大鼠。比较各组大鼠体重、肝重,空腹血糖、转氨酶、甘油三酯（TG）、总胆固醇（TC）、脂肪细胞因子,以及肝组织学改变。结果 12周后模型组大鼠肝组织病理学检查显示明显脂肪变,动物体重、肝重和各项生化指标均显著高于正常组;与模型组比,治疗组动物体重和生化指标均有改善,其中AST和TC下降有统计学意义（P〈0.05）;治疗组动物血清瘦素、抵抗素呈下降趋势,而脂联素呈升高倾向。结论多不饱和脂肪酸具有改善NASH大鼠糖脂代谢及脂肪细胞因子表达的能力。     

丹参对非酒精性脂肪性肝炎大鼠肝组织NF-κB、TNF-α表达的影响

[目的]研究肝组织NF-κB、TNF-α在非酒精性脂肪性肝炎(NASH)中的作用,并探讨丹参注射液对NASH大鼠的保护机制。[方法]采用高脂饮食16周建立大鼠NASH模型,每日予丹参注射液5ml/kg进行干预治疗,免疫组织化学法检测大鼠肝组织TNF-α表达。电泳迁移率改变分析检测大鼠肝组织NF-κB活性,观察丹参对NASH大鼠肝组织NF-κB、TNF-α表达的影响。[结果]与正常组相比,模型组大鼠肝组织NF-κB、TNF-α表达明显升高,丹参治疗后大鼠肝组织NF-κB、TNF-α较模型组明显降低。[结论]肝组织NF-κB、TNF-α表达增强与NASH的发生密切相关,丹参注射液能抑制NASH大鼠肝组织NF-κB、TNF-α表达,达到治疗NASH的目的。     

清肝化痰活血方对大鼠非酒精性脂肪性肝炎的防治作用

目的:探讨清肝化痰活血方对LXRa/FAS信号通路介导的非酒精性脂肪性肝炎(NASH)大鼠肝细胞脂肪沉积的影响。方法:选用SPF级雄性SD大鼠70只,分4组,正常组、模型组、治疗组及预防组;除正常组外其余3组大鼠采用高脂饮食复制NASH模型;造模8周结束。预防组大鼠从造模开始给予清肝化痰活血方灌胃,1次/d,共12周;治疗组大鼠从造模结束后,开始灌胃清肝化痰活血方,而模型组、正常组大鼠灌胃等量生理盐水,均1次/d,共4周。观察各组大鼠肝脏脂肪变性程度、血清ALT、AST、TC、TG水平。采用实时定量PCR法检测肝细胞LXRamRNA、FAS mRNA的表达。结果:造模8周时,正常组大鼠肝组织正常,其余3组大鼠肝脏均发生不同程度脂肪变性;模型组大鼠血清ALT、AST水平升高,与正常组比较,差异有显著性意义(P0.05),与模型组比较,预防组大鼠血清ALT、AST、TC、TG水平显著下降(P0.05);治疗组大鼠的肝脏脂肪变性程度均明显轻于模型组大鼠,其ALT、AST、TC、TG水平明显低于模型组(P0.05);与正常组比较,其余3组大鼠肝细胞LXRa、FAS基因表达水平均明显升高(P0.01),与模型组比较,预防组和治疗组大鼠的上述基因表达水平下调明显(P0.01)。结论:LXRa/FAS通路是介导NAFLD脂质平衡代谢紊乱重要的信号通路,清肝化痰活血方能够调控肝细胞LXRa/FAS通路,使NASH大鼠肝细胞脂肪沉积趋于减轻,这可能是该方抗实验性大鼠脂肪性肝炎的作用机制之一。     

非酒精性脂肪性肝炎大鼠血液流变学的改变

[目的]探讨非酒精性脂肪性肝炎(NASH)大鼠血液流变学的改变。[方法]健康雄性Wistar大鼠16只,随机分为正常组和模型组,分别以标准饲料和高脂饲料喂养,连续12周后处死大鼠,苏木精-伊红染色观察大鼠肝脏组织病理学变化,脂酶法检测肝组织匀浆三酰甘油(TG)、胆固醇(TC)水平,黄嘌呤氧化酶法检测血及肝组织匀浆中超氧化物歧化酶(SOD)水平,硫代巴比妥酸(TBA)法检测血及肝组织丙二醛(MDA)水平,锥板法检测血液流变学指标。[结果]模型组大鼠肝组织重度脂肪变,并伴有肝细胞气球样变,肝细胞碎屑样坏死、炎症细胞浸润和汇管区渗出;肝组织匀浆TG、TC水平较正常组明显升高(P<0.01);血清及肝组织匀浆中MDA水平均较正常组明显增高(P<0.05)、SOD活力均较正常组明显下降(P<0.05);全血黏度(高、中、低切)、全血还原黏度及红细胞聚集性指数明显高于正常组(P<0.01,<0.05),血浆黏度、红细胞刚性和红细胞变形指数2组之间差异无统计学意义(P>0.05)。[结论]高脂饲料诱导的NASH大鼠存在血液流变学指标的异常改变。     

复方甘草甜素脂质体干预大鼠非酒精性脂肪性肝炎的疗效观察

目的 观察复方甘草甜素脂质体对大鼠非酒精性脂肪性肝炎(NASH)的干预作用.方法 SD雄性大鼠35只随机分为4组,模型组、复方甘草甜素对照组和复方甘草甜素脂质体治疗组各10只,给予高脂饲料喂养,另设5只普通饲料喂养大鼠作为正常组.8周后开始腹腔内注射药物干预,16周后处死全部实验大鼠.全自动生化分析仪检测血清ALT、AST及GGT水平,参照2006年2月份的NAFLD诊疗指南中脂肪肝分度和炎症分级(NASH-F(0-4)G(0-3))的组织病理学标准进行量化计分.结果 与模型组相比,治疗组血清AST水平明显下降(P<0.05),血清GGT水平与肝组织炎症计分均显著下降(P<0.01);与对照组比较,治疗组肝组织炎症计分及血清GGT水平均显著降低(P0.01).结论 复方甘草甜素脂质体对高脂饮食诱发的大鼠脂肪性肝炎有一定的防治作用.     

二陈汤与苓桂术甘汤治疗非酒精性脂肪性肝病炎性损伤的机制研究

[目的]探讨经验方二陈汤与苓桂术甘汤对高脂饲料诱导大鼠非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)分子作用机制。[方法]以高脂饲料喂养40只雄性SD大鼠8周,随机分为正常组、模型组、罗格列酮组、二陈汤组、苓桂术甘汤组,于第9周起分别给予罗格列酮剂量1mg·kg-1、二陈汤4.52g·kg-1、苓桂术甘汤组3.31g·kg-1治疗4周。12周后将大鼠处死并观察药物对大鼠肝功能的影响,并对肝组织进行常规苏木精-伊红染色,观察病理改变;Western blot检测二陈汤与苓桂术甘汤以及两方含药血清对NASH大鼠肝组织以及经软脂酸刺激肝细胞的肿瘤坏死因子TNF-α与核转录因子NF-κB蛋白表达的影响。MTT法检测不同浓度软脂酸对大鼠肝细胞增殖的影响,以及二陈汤与苓桂术甘汤含药血清对软脂酸的拮抗作用。[结果]与模型组比较,罗格列酮和苓桂术甘汤可有效降低NASH大鼠血清ALT、AST(P0.05),同时改善肝脂肪变性的严重程度和降低TNF-α和NF-κB蛋白的表达(P0.05)。与模型组比较,虽然二陈汤治疗后NASH大鼠肝组织TNF-α和NF-κB蛋白表达显著性下降(P0.05),但是血清ALT、AST并未显著性降低(P0.05),苓桂术甘汤含药血清能明显改善软脂酸对肝细胞增殖的抑制(P0.05)。与模型组比较,二陈汤与苓桂术甘汤含药血清均能抑制软脂酸刺激的肝细胞TNF-α和NF-κB蛋白表达(P0.05)。[结论]罗格列酮、二陈汤、苓桂术甘汤能改善大鼠肝脏脂肪变性,降低TNF-α和NF-κB蛋白表达。软脂酸可以明显抑制肝细胞增殖率,罗格列酮与苓桂术甘汤含药血清能拮抗软脂酸对肝细胞增殖的抑制。苓桂术甘汤通过抑制NF-κB蛋白表达,减少TNF-α表达,从而减轻肝脏炎性损伤,进而达到治疗NASH的作用。     

当飞利肝宁胶囊改善高脂饮食联合四氯化碳诱导的大鼠非酒精性脂肪性肝炎的作用机制

目的研究当飞利肝宁胶囊对高脂饮食联合四氯化碳(CCl4)诱导的大鼠非酒精性脂肪性肝炎(NASH)防治作用及机制。方法雄性Wistar大鼠,随机分为正常对照组、NASH模型组和当飞利肝宁胶囊治疗组。正常组大鼠喂食普通饲料,模型和治疗组给予高脂饲料,治疗组同时每天予当飞利肝宁胶囊灌胃干预。8周后,除正常组外,其余大鼠腹腔注射CCl4,48 h后处死并收集血清和肝脏组织。观察肝脏组织病理学改变,检测血清ALT、AST、乳酸脱氢酶(LDH)、总胆红素(TBil)、胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和游离脂肪酸(FFA)水平,检测血清空腹血糖(FBG)、空腹胰岛素(FIN)并计算HOMA指数,以及血清脂联素和肝组织肿瘤坏死因子(TNFα)含量。结果肝组织油红O染色显示,模型组出现大面积小叶内肝细胞脂肪变性,HE染色同时显示出肝细胞气球样变性和炎性细胞浸润,而治疗组肝细胞脂肪变性、气球样变和炎性浸润明显减轻。模型组血清ALT、AST、LDH、TG、LDL、FFA水平较正常组显著升高(P<0.05),HOMA指数和肝组织TNFα含量也显著升高(P<0.05),血清脂联素含量明显下降;治疗组大鼠上述指标均显著改善(P<0.05)。结论当飞利肝宁胶囊对高脂饮食联合CCl4诱导的大鼠NASH具有显著防治作用,对脂联素、TNFα表达水平的调节和改善胰岛素抵抗是其重要机制。     

节制饮食对大鼠非酒精性脂肪性肝炎的治疗作用

非酒精性脂肪性肝病 (nonalcoholicfattyliverdiseases ,NAFLD)可发展为肝纤维化和肝硬化 ,且经过非酒精性脂肪性肝炎 (nonalcoholicsteatohepatitis ,NASH )这一病理阶段[1 3 ] ,因而早期干预是必要的。然而至今尚无治疗NAFLD的特效药物 ,因此作为基本治疗的饮食疗法在NAFLD治疗中的作用越发受到重视。本研究将观察节制饮食对NASH的治疗作用。材料与方法一、材料雄性SD大鼠 2 0只 ,购自西普尔 必凯公司 ,体重 14 0～160 g ,正常喂养 1周后 ,通过高脂饮食 12周建立NASH大鼠模型 ,随机分为 2组 :模型组 10只继予高脂饮食喂养 ;…     

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.     

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.     

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.     

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.