甘草酸二铵脂质配位体治疗高脂饮食大鼠非酒精性脂肪性肝病疗效观察

非酒精性脂肪性肝病（NAFLD）的诊断和治疗是目前肝病研究的重点和热点之一,但由于其病因繁多且发病机制尚不十分明确,目前临床上尚无治疗此病的满意药物。甘草酸二铵脂质配位体已初步应用于临床辅助治疗多种慢性肝病,但关于其治疗MAFLD的研究报道少见,本研究通过建立高脂饮食大鼠NAFLD模型,观察甘草酸二铵脂质配位体对大鼠NAFLD的治疗效果。     

甘草酸二铵脂质配位体对非酒精性脂肪性肝病大鼠肝组织AMPK信号通路的影响*

目的 研究甘草酸二铵脂质配位体（DGLL）对非酒精性脂肪性肝病（NAFLD）大鼠的治疗作用,并探讨其可能的作用机制。方法 以高脂饲料喂养建立NAFLD大鼠模型,在造模成功后分别给予DGLL或多烯磷脂酰胆碱（PPC）灌胃16周。采用免疫组化法检测肝组织磷酸化的磷酸腺苷激活蛋白激酶α（P-AMPKα）蛋白表达,采用Real-time PCR法检测肝组织过氧化物酶体增殖物激活受体γ（PPAR-γ）、肉毒碱棕榈酰基转移酶-1（CPT-1）、葡萄糖转运蛋白4（GLUT-4）、酰基辅酶A氧化酶（ACO）、肝脏型脂肪酸结合蛋白（L-FABP）、乙酰辅酶A羧化酶（ACC）mRNA。结果 DGLL组血清瘦素为（3.87±0.38）ng/ml,显著低于模型组【（4.68±0.39）ng/ml,P<0.01】或PPC组【（4.55±0.24）ng/ml,P<0.01】;DGLL组脂联素为（12.27±0.64）μg/ml,显著高于模型组【（10.46±0.28）μg/ml,P<0.01】,但与PPC组【（12.13±0.56）μg/ml,P>0.05】比,无统计学差异;DGLL组大鼠肝组织P-AMPKα蛋白阳性表达面积为（8.38±3.27）%,显著高于模型组【（1.81±0.90）%,P<0.01】或PPC组【（5.50±0.73）%,P<0.05】;DGLL组肝组织PPAR-γ、CPT-1、GLUT-4 mRNA水平分别为（1.07±0.14、0.91±0.05、1.61±0.54）,显著高于模型组【分别为（0.26±0.12、0.14±0.01、0.10±0.03,P<0.05】,但ACO mRNA水平（0.23±0.09）与模型组比,无统计学差异【（0.24±0.02）,P>0.05】;PPC组PPAR-γ和CPT-1 mRNA水平分别为（0.65±0.16）和（0.22±0.05）,显著低于DGLL组（P<0.05）,而GLUT-4和ACO mRNA水平（1.32±0.12和0.14±0.05）与DGLL组比,无统计学差异（P>0.05）;DGLL组肝组织ACC mRNA水平为（1.67±0.23）,显著低于模型组【（3.31±0.02）,P<0.05】或PPC组【（2.69±0.14）,P<0.05】;DGLL组L-FABP mRNA水平为（1.06±0.04）,显著低于模型组【（1.26±0.02）,P<0.05】,而与PPC组【（1.06±0.09）,P>0.05】比,无统计学差异。结论 DGLL能降低NAFLD大鼠血脂、血糖、胰岛素、HOMA-IR、瘦素水平,升高脂联素,并增加肝组织P-AMPKα蛋白表达,上调PPAR-γ、CPT-1、GLUT-4 mRNA水平、下调L-FABP和ACC mRNA水平,这些作用可能与其激活AMPK通路和改善NAFLD糖脂代谢紊乱有关。     

复方甘草酸苷联合中药汤剂治疗非酒精性脂肪肝临床观察

目的观察复方甘草酸苷联合中药汤剂治疗非酒精性脂肪肝的临床疗效。方法非酒精性脂肪性肝病60例随机被分为治疗组和对照组各30例,分别以复方甘草酸苷联合中药汤剂治疗及单纯复方甘草酸苷治疗,疗程8周,治疗后比较两组疗效。结果治疗组的临床症状腹胀、胁痛、纳呆、乏力等的改善情况,谷丙转氨酶（ALT）、谷草转氨酶（AST）等肝功能恢复程度及甘油三酯（TG）、总胆固醇（TC）等血脂下降程度均明显优于对照组（P〈0.05）,治疗组总有效率为90%,对照组总有效率为73.3%（P〈0.05）。结论复方甘草酸苷联合中药汤剂治疗非酒精性脂肪肝效果明显。而抗脂质过氧化,稳定肝细胞膜,纠正肝内脂质代谢紊乱,调节免疫功能,抗肝纤维化,促进脂肪在肝内代谢的作用可能是其作用机理。     

左卡尼汀联合甘草酸二铵治疗非酒精性脂肪性肝病

左卡尼汀又称左旋肉毒碱,是哺乳动物能量代谢中的必需物质,其主要功能是促进脂类代谢.动物实验证明,左卡尼汀能改善大鼠肝脏脂肪变性.甘草酸二铵注射液对各种急、慢性肝炎、肝硬化以及理化因素引起的肝功能损害具有较好的临床疗效.本研究采用左卡尼汀联合甘草酸二铵治疗非酒精性脂肪性肝病（NAFLD）,并以甘草酸二铵作为对照组,对两种方案的肝功能、血脂和B超脂肪肝声像图改善情况进行对比研究.     

异甘草酸镁治疗慢性乙型肝炎临床观察

异甘草酸镁具有很强的抗炎、保护肝细胞膜作用,对慢性肝病有很好的疗效。我们应用异甘草酸镁注射液治疗慢性乙型肝炎（CHB）40例,并与甘草酸二铵注射液进行疗效比较,现报道如下。[第一段]     

八仙长寿汤对小鼠脑、肝脂质过氧化作用的影响

目的探讨八仙长寿汤对小鼠脑、肝抗脂质过氧化的作用。方法采用硫代巴比妥酸反应法，观察了八仙长寿汤对小鼠在体和体外肝脏与脑组织匀浆及四氯化碳（CCl4）引起的脂质过氧化作用的影响，同时观察了对小鼠血清谷丙转氨酶（ALT）的影响。结果八仙长寿汤对小鼠体内和体外及CCl4诱导产生的脑、肝组织中的丙二醛（MDA）生成量均有不同程度的降低作用且有量效关系，不同剂量的八仙长寿汤还能减轻CCl4对肝脏的损害。结论八仙长寿汤能降低脑和肝脏的脂质过氧化作用，可减少MDA的生成。     

丹芍化纤胶囊抗肝纤维化治疗对大鼠过氧化物酶体增殖物激活受体-γ表达的影响

过氧化物酶体增殖物激活受体-γ（PPAR-γ）是调节脂质代谢的重要因子，越来越多的研究显示，它在肝纤维化进程中也有不可低估的作用。HSC是肝纤维化形成过程中的重要细胞。我们观察了解CCl4中毒性肝纤维化大鼠肝脏组织PPAR-γ和α-平滑肌肌动蛋白（α-SMA）的表达及其在中药复方制剂丹芍化纤胶囊抗肝纤维化治疗后的变化。[第一段]     

甘草酸二铵治疗儿童慢性乙型肝炎的疗效观察

目的观察口服甘草酸二铵（甘利欣）胶囊治疗儿童慢性乙型肝炎的疗效。方法 29例慢性乙型肝炎患儿口服甘利欣胶囊,27例口服护肝片3个月。结果甘利欣组治疗后血清ALT、AST、TBIL水平均明显降低,与治疗前比较差异有高度显著性（P〈0.01）;甘利欣组治疗后血清HA、LN、ⅣC、PⅢNP水平与对照组比较差异有显著性降低（P〈0.05）。结论甘利欣具有保肝和抗肝纤维化作用。     

谷胱甘肽联合甘草酸二铵治疗酒精性肝硬化72例临床观察

目的观察谷胱甘肽联合甘草酸二铵对酒精性肝硬化的疗效。方法本组72例均为本院2004年7月—2007年12月住院患者，符合酒精性肝硬化的诊断标准，随机分为对照组36例，给予基本相同的护肝、支持、对症治疗。治疗组36例，在此基础上加用谷胱甘肽、甘草酸二铵治疗。结果治疗组的临床症状改善明显，食欲不振、乏力等症状减轻，体重增加，总胆红素下降明显，各项实验室检查结果较对照组差异有显著性（P〈0．01）。结论谷胱甘肽联合甘草酸二铵治疗酒精性肝硬化疗效显著，值得临床推广。     

还原型谷胱甘肽联合甘草酸二铵治疗抗结核药物所致的肝损害

目的观察还原型谷胱甘肽联合甘草酸二铵治疗抗结核药物所致的肝损害的临床疗效。方法80例抗结核药物所致的轻中度肝损害患者,随机分为两组,对照组38例给予甘草酸二铵、维生素C、肌苷等常规治疗;治疗组42例在常规治疗基础上加用5%葡萄糖注射液250ml 还原型谷胱甘肽1.8静滴qd疗程3周。结果治疗后两组患者临床症状及肝功能各项指标均有不同程度改善(P<0.01)且治疗组明显优于对照组(P<0.01)。结论还原型谷胱甘肽联合甘草酸二铵在不停用抗结核药物治疗下,对抗结核药物所致的轻中度肝损害能较快使肝功能恢复正常,比单独应用甘草酸二铵有显著疗效。     

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.     

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.     

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.     

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.