二甲双胍的抗炎作用及其糖尿病肾脏保护作用

炎性反应在糖尿病肾病(DN)的发生、发展中起重要作用.高糖作为始动因素,与晚期糖基化终末产物(AGEs)、氧化应激及肾内血流动力学的改变共同引起了糖尿病肾脏炎性反应的发生.而二甲双胍作为治疗糖尿病的一线药物,近年研究显示其除降糖作用以外,还可通过激活腺苷酸活化蛋白激酶(AMPK)、抗氧化应激和改善胰岛素抵抗等机制发挥抗炎作用,从而预防和延缓DN的发生和发展.     

柚皮苷对糖尿病肾脏疾病的作用机制

糖尿病肾脏疾病(DKD)是糖尿病最严重的慢性并发症之一.目前认为DKD的发生、发展是多因素共同作用的结果,包括氧化应激、炎性反应、纤维化以及自噬等,而其中高血糖是最关键的,它是发生肾脏损害的先决条件.柚皮苷(4',5,7-三羟二氢黄酮-7-鼠李葡萄糖苷)是一种从芸香科柑橘属植物柚中提取的双氢黄酮类化合物,具有多种药理活性,如抗炎、抗氧化应激、改善胰岛素抵抗、调节糖、脂代谢、抗纤维化等,可能从根本上延缓DKD的进展.     

雷公藤治疗糖尿病肾病的机制及其毒性研究进展

糖尿病肾病(DKD)是糖尿病严重的微血管并发症,致残及致死率高,治疗效果差。DKD发病机制不明确,但炎症反应在其发生、发展过程中的作用不容忽视。雷公藤具有独特的抗炎和免疫抑制作用,加上其对血糖影响较小,近年来广泛用于DKD治疗,已成为临床研究的热点。本文从免疫抑制、抑制炎症细胞浸润及细胞因子表达、改善氧化应激、保护足细胞等方面阐述雷公藤治疗DKD的机制及其毒性方面的研究进展。     

血管紧张素Ⅱ、炎性反应和2型糖尿病

以往临床研究发现高血压病患者发生2型糖尿病的风险增加,阻断肾素-血管紧张素系统(RAS)对于预防2型糖尿病的发生具有一定的保护作用.近期研究还表明,RAS可能直接参与了糖尿病发生发展过程.炎性反应是肥胖、2型糖尿病等代谢性疾病的重要分子基础.血管紧张素介导的氧化应激、炎性反应水平以及游离脂肪酸的增加在局部和全身都对机体产生重要的影响.     

MiRNA-150与糖尿病肾病

糖尿病肾病以肾间质纤维化和肾脏硬化为病理学特点,慢性低度炎性反应、氧化应激、新生血管形成、内皮功能紊乱等在糖尿病肾病的发生和发展中起重要作用.MiRNA-150参与多种炎性反应、调节炎性反应信号通路,在肾脏纤维化中表达升高,而且可以通过微泡促进新生血管形成,进而导致肾间质纤维化,肾脏硬化;其靶基因,如细胞因子信号转导抑制蛋白1 (SOCS1)、基质细胞衍生因子-1(SDF-1)/趋化因子受体4(CXCR4)等在糖尿病肾病中起保护作用.因此,miRNA-150可能通过影响其下游信号分子的表达在糖尿病肾病的发生、发展中起重要作用.     

腺苷酸活化蛋白激酶在脑缺血中的作用及其机制

腺苷酸活化蛋白激酶(AMPK)是一种高度保守的丝氨酸/苏氨酸蛋白激酶,在能量代谢的调控中起重要作用。脑缺血、缺氧后可激活AMPK,活化的AMPK通过抑制氧化应激和炎性反应、激活自噬、减轻细胞凋亡和促进血管生成等机制,减轻脑缺血后的神经功能损伤,从而发挥神经保护作用。作者对AMPK的分子生物学特征及其在脑缺血中的作用及机制进行了综述,目的在于促进对AMPK的深入研究,使其成为缺血性卒中治疗的一个新靶点。     

细胞焦亡在糖尿病肾病发病机制中作用的研究进展

糖尿病肾脏病(DKD)是糖尿病患者最主要的微血管并发症之一,其发病机制主要与代谢紊乱、血流动力学异常、氧化应激等有关,炎性反应贯穿于DKD全过程。细胞焦亡(pyroptosis)是新发现的一种细胞死亡形式,由NOD样受体蛋白3(NLRP3)炎症小体激活,依赖半胱氨酸蛋白水解酶(caspase)-1/4/5/11,通过G...     

慢性低度炎性反应与糖尿病肾脏疾病的相关性分析:一项大样本病例-对照研究

目的 探讨慢性低度炎性反应与糖尿病肾脏疾病(DKD)的关系.方法 将1254例2型糖尿病患者分为DKD组(487例)与单纯T2DM组(767例),DKD诊断依据:符合估算的肾小球滤过率(eGFR)＜ 60 mL/(min·1.73 m2)或尿微量白蛋白/肌酐比值(UACR) ≥30 mg/g.通过自动分析仪测定血清慢性低度炎性反应指标:超敏C反应蛋白(hs-CRP)、白细胞总数、中性粒细胞百分比(NCR),并记录性别、病程、收缩压、舒张压等指标.利用多元Logistic回归分析慢性低度炎性反应指标与DKD的关系.结果 与单纯T2DM组相比,DKD组的hs-CRP、白细胞总数、NCR均显著升高(t=-3.60、-3.43、3.10,P均＜0.01).多元Logistic回归分析显示,hs-CRP(OR=1.116,95％ CI:1.042 ～1.195,P=0.002)、白细胞总数(OR=1.092,95％ CI:1.002 ～1.189,P=0.044)和NCR(OR =1.018,95％ CI:1.004～ 1.033,P=0.015)与DKD风险增加显著相关.结论 DKD的慢性低度炎性反应指标显著升高,hs-CRP、白细胞总数、NCR是DKD的独立危险因素.     

TXNIP与糖尿病及其并发症的关系

硫氧还蛋白(TRX)相互作用蛋白(TXNIP)在氧化还原、细胞增殖、细胞凋亡、血脂和血糖代谢等过程中发挥多重作用.大量研究表明,高糖可以通过碳水化合物反应元件结合蛋白(ChREBP)、p38丝裂原活化蛋白激酶(p38 MAPK)、叉头框转录因子O亚族1(FOXO1)途径引起TXNIP表达增多,过多的TXNIP主要通过介导氧化应激和炎性反应两条途径引起胰岛β细胞损害、胰岛功能下降及胰岛素抵抗.且TXNIP在糖尿病视网膜病变、糖尿病肾病的发生、发展中也起重要作用.     

Krüppel样转录因子9在糖尿病肾脏病中的研究进展

糖尿病肾脏病(DKD)是糖尿病的重要并发症, 可发展为终末期肾病, 其发生发展与高血糖、氧化应激、炎症等导致的肾脏纤维化相关, 早期诊断及干预可延缓DKD进展, 但目前仍有诸多局限。近年来, 寻找DKD特异性的生物标志物协助早期诊断、探索新的治疗靶点已成为研究热点。Krüppel样转录因子(KLF)家族是一类与真核细胞的转录调控密切相关的转录家族, 参与细胞增殖、分化和凋亡等多个生命过程的调控, 其家族成员KLF9是一种能调控机体多种途径、发挥不同生物学作用的转录因子, 参与多种系统疾病的发生发展。越来越多的研究表明, KLF9可以调节与糖尿病/肥胖诱导的肾脏疾病及其细胞凋亡、炎症、氧化应激等相关的多种途径, 在糖尿病及其并发症中起到关键的调节作用, 但目前KLF9在DKD中的相关研究尚未见系统综述报道。该文重点从机体糖脂代谢紊乱、氧化应激、免疫炎症等病理生理过程为切入点, 系统综述KLF9在DKD中的研究进展, 以提高临床对KLF9与DKD发生发展相关性的认识。     

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.