水飞蓟素对大鼠非酒精性脂肪性肝炎的防治作用及机制

目的研究水飞蓟素对大鼠非酒精性脂肪性肝炎的治疗作用及部分机制研究。方法将30只大鼠随机分为3组（正常对照组、病理模型组、水飞蓟素组），利用高脂饮食联合氧四环素腹腔注射建立大鼠脂肪肝模型，水飞蓟素组给予水飞蓟素干预（100mg／kg），8周后处死所有大鼠，检测大鼠血清丙氨酸转氨酶（ALT）、甘油三酯（TC）、总胆固醇（TG）、丙二醛（MDA）、超氧化物歧化酶（SOD）、肝组织TG、TC、MDA、SOD水平及采用半定量逆转录聚合酶链反应（RT-PCR）检测肝脏过氧化物酶体增殖物激活受体α（PPARα）mRNA的表达情况。结果与正常对照组相比，模型组大鼠血清ALT，TG，TC，MDA和肝组织的TG，TC、MDA明显升高，而血清及肝组织的SOD明显降低。肝组织PPARetmRNA表达减少（P〈0．01）。与模型组比较，水飞蓟素组大鼠血清ALT，TG，TC，MDA和肝组织的TG，TC，MDA明显降低。而血清及肝组织的SOD明显升高，肝组织PPARαmRNA表达增加（P〈0．01）。结论水飞蓟素对实验性非酒精性脂肪肝大鼠具有一定的治疗作用，其作用机制之一是促进肝脏PPARα表达。     

肝康Ⅳ号对大鼠酒精性脂肪肝的保护作用

[目的]探讨肝康Ⅳ号对大鼠酒精性脂肪肝的保护作用。[方法]采用高脂饮食和白酒诱导大鼠酒精性脂肪肝模型,以不同剂量肝康Ⅳ号煎液灌胃治疗（治疗组）,于8周末处死鼠,采血检测血清天冬氨酸转氨酶（AST）、丙氨酸氨基转移酶（ALT）及肝脏总胆固醇（TC）、三酰甘油（TG）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平,肉眼和显微镜下观察肝组织病理学变化及脂肪变程度计分,并与空白对照组、模型组和东宝肝泰组比较。[结果]模型组肝组织明显脂肪变性,治疗组和东宝肝泰组可显著降低血清AST、ALT和肝组织TC、TG、MDA水平,提高肝组织SOD活性,肝康Ⅳ号治疗效果优于东宝肝泰;肝组织病理检查显示,肝康Ⅳ号可减轻肝组织脂肪变和点灶样坏死,镜下计分显示肝康Ⅳ号中、高剂量组对肝组织改善优于东宝肝泰组。[结论]肝康Ⅳ号可对抗氧化应激和脂质过氧化损害,对大鼠酒精性脂肪肝有良好的治疗效果。     

低铁负荷对大鼠非酒精性脂肪性肝炎的影响

目的研究非酒精性脂肪性肝炎（NASH）大鼠肝铁负荷的变化及低铁负荷对大鼠NASH的影响。方法SD雄性大鼠随机分为4组：正常对照组1、低铁对照组2、模型组3、低铁模型组4。实验的12周末观察血清胆固醇（TG）、甘油三酯（TC）、转氨酶（ALTAST）、血清铁（SI）、过氧化物歧化酶（SOD）、丙二醛（MDA）的含量以及肝匀浆铁、TG、TC、SOD、MDA的含量,观察肝组织病理学改变的特点。结果与正常对照组相比,模型组血清TG、TC、ALT、AST、MDA的含量明显升高,SOD的含量明显降低,血清铁含量升高不明显;肝匀浆TG、TC、ALT、AST、MDA及铁的含量明显升高,肝匀浆SOD的含量明显降低。与模型组相比,低铁模型组血清TG、TC、ALT、AST、SI、MDA含量明显降低,SOD的含量明显升高;肝匀浆TG、TC、SI、MDA含量明显降低,SOD含量明显升高。肝脏病理学切片示：模型组大鼠肝小叶内脂滴比率大于三分之一,造模成功,低铁模型组大鼠肝脏的炎症活动度计分及铁染色计分明显低于模型组。结论NASH大鼠肝脏铁负荷增加,低铁负荷可以减轻大鼠NASH的损伤程度。     

清肝降浊颗粒对酒精合并高脂饮食性脂肪肝大鼠的治疗作用

目的研究清肝降浊颗粒对酒精与高脂饲料联合诱导的大鼠脂肪肝是否具有治疗作用。方法采用灌服56%乙醇同时饲喂高脂饲料的方法,诱导建立复合因素导致的脂肪肝大鼠模型。给药4 w后,检测与酒精性脂肪肝密切相关的各项指标。血液生化学指标检测:天冬氨酸氨基转移酶(AST)活性,丙氨酸氨基转移酶(ALT)活性;血清及肝组织中总胆固醇(TC)含量,甘油三酯(TG)含量;肝脏组织中超氧化物歧化酶(SOD)活性,丙二醛(MDA)含量;肝脏、脾脏、胸腺及肾上腺脏器系数。结果清肝降浊颗粒对脂肪肝动物血清AST、ALT、TC和TG水平的异常升高均具有明显的降低作用(P0.01或P0.05);可以升高脂肪肝动物肝组织中SOD活性,降低TC、TG和MDA含量及肝脏系数(P0.01或P0.05)。结论清肝降浊颗粒具有保肝降酶、抑制脂质过氧化反应、降低血脂肝脂含量,从而达到治疗复合因素所致脂肪肝的作用。     

谷氨酰胺对非酒精性脂肪肝炎大鼠肠黏膜屏障的保护作用

目的 探讨谷氨酰胺对非酒精性脂肪肝炎肠黏膜屏障功能的保护作用.方法 32只SD大鼠随机分为正常对照组8只,给予普通饮食喂养;高脂饮食组24只,给予高脂饲料喂养,于8周末从高脂饮食组随机抽取8只大鼠处死作为单纯性脂肪肝组,剩余大鼠随机分为谷氨酰胺组、NASH组,谷氨酰胺治疗组在8周末加用谷氨酰胺灌胃.12周末处死所有大鼠,测定大鼠门静脉血浆中内毒素、腹主动脉血浆中D-木糖以及肠粘液中sXgA的水平,测定小肠组织匀浆中SOD的活性和MDA的含量,并测定大鼠血清中TC、TC、ALT、AST,HE染色观察肝脏病理改变.结果 12周模型组大鼠血清ALT、AST明显升高,肝脏病理表现为脂肪性肝炎,谷氨酰胺治疗组大鼠血清ALT、AST明显下降(P＜0.05),肝组织炎症活动计分也明显下降(3.25±1.49 vs.4.38±1.06,P＜0.05),但仍显著高于8周单纯性脂肪肝组大鼠水平(3.25±1.49 vs.2.00±0.76,P＜0.05).谷氨酰胺治疗组肝细胞脂肪变性程度无显著变化.谷氨酰胺治疗组大鼠门静脉血浆中内毒素、腹主动脉血浆中D-木糖、小肠组织匀浆中MDA含量与模型组相比明显降低(P＜0.05).肠黏液中slgA的水平和小肠组织匀浆中SOD与模型组相比明显升高(P＜0.05).结论 谷氨酰胺可以降低高脂饮食诱发的非酒精性脂肪性肝炎大鼠血清中转氨酶水平和肝组织炎症损伤,降低门静脉血中内毒素水平,但不能完全阻止炎症的进展,提示肠黏膜屏障功能的改变是非酒精性脂肪性肝炎发病的重要机制之一.     

甘正复方对大鼠非酒精性脂肪肝的影响

[目的]研究甘正复方对大鼠非酒精性脂肪肝模型形成的影响.[方法]30只SD大鼠随机分为3组(各10只):正常组喂普通饲料;模型组和治疗组喂高脂饲料.治疗组高脂饮食12周后同时给予甘正复方治疗.16周处死大鼠.测定血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、丙二醛(MDA)、超氧化物歧化酶(SOD)活性;苏木精-伊红染色观察肝脏病理改变;免疫组化法测定细胞色素P450ⅡE1(CYPⅡE1)及过氧化物酶体增殖物激活受体α(PPARα)表达.[结果]模型组血清ALT、AST、TC、TG及MDA增加,SOD减少;免疫组化示CYPⅡE1表达增高,PPARα表达明显减少;肝脏组织出现脂肪变性和炎症坏死.治疗组较模型组血清ALT、AST及TG、MDA均下降,SOD增加,CYPⅡE1表达减少,肝脏脂肪变性和炎症坏死的程度明显减轻.[结论]甘正复方能通过调节TG代谢、抗氧应激和脂质过氧化有效地治疗大鼠脂肪肝.     

酒精性脂肪肝大鼠肝组织骨桥蛋白表达的变化

目的探讨乙醇联合高脂饮食诱导脂肪肝大鼠肝组织骨桥蛋白（OPN）表达的变化。方法采用高脂饮食联合乙醇灌胃制备大鼠脂肪肝模型。在第6周末分别取血和肝组织,常规检测血生化指标和采用Westernblot法检测大鼠肝组织骨桥蛋白表达的改变。结果乙醇联合高脂饮食条件下大鼠血清ALT、AST、TG、TC水平升高（P〈0．05）,HDL-C降低（P〈0．05）;油红O染色结果显示乙醇联合高脂饮食组大鼠肝脏脂肪变明显;模型组大鼠肝组织OPN蛋白表达明显增强（P〈0．05）。结论骨桥蛋白表达增强在大鼠乙醇性脂肪肝的发病过程中起一定的作用。     

橙皮苷对四环素所致小鼠脂肪肝的保护作用

目的：观察橙皮苷对四环素引起小鼠非酒精性脂肪肝的保护作用。方法将ICR小鼠分为A、B、C组, A组给予橙皮苷（300 mg／kg）连续灌胃10 d,B、C组给予同体积溶剂;在第10天给药后1 h时A、B组腹腔注射四环素200 mg／kg 20 mL,C组给予相同pH值等体积生理盐水。给毒后24 h眼球取血,并取肝脏,检测血清ALT、AST、TG、TC及肝组织TG、TC、丙二醛（MDA）、超氧化物歧化酯（SOD）、谷胱甘肽（GSH）,HE染色观察肝脏组织病理学改变。结果与C组比较,B组血清ALT、AST升高而TG、TC降低,肝组织中TG、TC、MDA、GSH升高,P均＜0．05;与B组比较,A组血清ALT、AST降低而TG、TC升高,肝组织中TG、TC降低而GSH升高,P均＜0．05。 C组小鼠肝脏未见明显病变,B组动物肝脏的中央静脉和小叶间静脉周围出现肝细胞肿胀、水样变性等病理改变。 A组给药可减轻上述病理改变。结论橙皮苷对四环素所致小鼠脂肪肝具有明显的保护作用。     

降脂护肝胶囊治疗非酒精性脂肪性肝病的实验研究

目的:探讨降脂护肝胶囊对非酒精性脂肪性肝病(NAFLD)的疗效.方法:采用高胆固醇高脂饮食喂养,复制NAFLD大鼠模型,设降脂护肝胶囊治疗组(Z组)、模型组(M组)及空白对照组(K组),检测各组大鼠血清ALT、AST、TG、TC、TNF-α、IFN-γ水平及肝组织SOD活性、MDA浓度,观察肝脏组织病理学变化.结果:M组大鼠ALT、AST、TG、TC、MDA、TNF-α、IFN-γ水平明显升高,而SOD表达下降,与K组比较,差异有显著性意义(P<0.01或P<0.05);Z组大鼠的8次指标检测结果均得到明显改善,与M组比较,差异有显著性意义(P<0.01或P<0.05).M组大鼠肝脏脂肪变明显,且有散在坏死灶及炎性细胞浸润;Z组大鼠肝脏脂肪变比M组明显减轻,肝窦基本正常,无炎性细胞浸润.结论:降脂护肝胶囊能显著改善非酒精性脂肪肝大鼠的肝功能,降低血脂,提高肝细胞SOD活性,降低MDA含量,抑制炎症反应中细胞因子TNF-α、IFN-γ,改善肝组织学病理情况,对非酒精性脂肪性肝病有较好的治疗效果.     

复方甘枣宁预防大鼠非酒精性脂肪肝的实验研究

[目的]研究复方甘枣宁对高脂饮食诱发的大鼠脂肪肝的预防作用.[方法]采用高脂饲料喂饲制作大鼠非酒精性脂肪肝模型,同时以复方甘枣宁灌胃,12周后检测血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)水平,并作病理组织学观察,同时称体重、肝脏重,计算肝指数.[结果]复方甘枣宁明显减轻肝组织内脂肪变性,降低血清TC与AST水平.[结论]复方甘枣宁对高脂饮食诱发的大鼠非酒精性脂肪肝具有一定的预防作用.     

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.