TNF-a、IL-6在全身炎症反应综合征表达的研究进展

全身炎症反应综合征（Systemic inflammatory response syndrome, SIRS）是机体对多种细胞因子和炎症介质所产生的全身反应。由于感染、创伤、组织坏死和组织缺血等原因,诱发的一种系统性炎症反应,使机体处于高代谢、高动力循环及低外周血管阻力等状态。过度的炎性反应表现为高氧耗量、高通气量、高血糖、蛋白代谢增加、负氨平衡及高乳酸血症等。     

什么是炎症?炎症发生的原因是什么?

答:炎症是临床常见的一个病理过程,也是机体的一种抗病反应,可发生于机体各部位的组织和器官.例如毛囊炎、扁桃体炎、肺炎、肝炎和肾炎等.急性炎症通常具有红、肿、热、痛和机能障碍等变化,同时往往伴有发热,白细胞增多等全身反应.致炎因子作用于机体后,一方面引起组织细胞的损害,使局部组织细胞发生变性、坏死;另一方面,激起机体抗病机能增强,以利于消灭致炎因子,使受损害的组织得以修复.     

T淋巴细胞抑制急性感染的炎症反应

炎症反应是机体针对损伤因子所产生的防御反应并伴随着红、热、肿、痛的局部临床特征.炎症反应是由多种细胞和细胞因子共同参与的复杂过程,天然免疫细胞(包括吞噬细胞、自然杀伤细胞、巨噬细胞等)是起始和推进炎症反应的重要效应细胞,而获得性免疫细胞如T细胞不仅参与后期炎症反应的发生同时还具有调节早期炎症反应的重要功能.炎症反应本身有利于清除消灭致病因子,液体的渗出可稀释毒素,吞噬搬运坏死组织以利于再生和修复,使致病因子局限在炎症部位而不致蔓延全身.另一方面,过激和长期的炎症反应又会对机体造成损伤.因此,深入研究炎症反应的机制可为治疗炎症所引起的疾病提供新的思路.     

炎症反应的负性调控机制

炎症反应在机体自稳中发挥着重要的调节作用。炎症反应可以消除入侵的病原微生物,清除坏死组织,促进组织修复。但过度的炎症反应也会导致组织细胞的变性坏死。因此炎症反应的负性调控对内环境的自稳和机体的生存至关重要。本文就炎症反应的主要信号转导通路,miRNA、蛋白修饰、自噬等对炎症反应的负性调控及负性调控异常在炎症性疾病中的作用作一简要综述。     

术中回收式自体输血与全身炎症反应研究进展

术中回收式自体输血技术被大量临床研究表明对机体是安全的、有效的,但在一些研究中发现回输的自体血中含有炎性因子,其可能对机体的全身炎症反应产生不利影响。本文就近年来有关术中回收式自体输血与全身炎症反应研究作一综述。     

肠-肝轴与非酒精性脂肪性肝病

肠道菌群组成和数量的改变影响宿主的能量代谢、免疫应答和炎症反应状态。非酒精性脂肪性肝病患者常伴有小肠细菌过度生长或某些菌群种类和数量的改变,以及肠道黏膜通透性增加。肠道细菌通过增强肝脏脂肪合成、诱导机体胰岛素抵抗、激活天然免疫系统相关分子模式等机制,诱发肝脏炎症反应,启动纤维化进程,促进单纯性脂肪变向脂肪性肝炎发展。鉴定影响机体能量代谢和炎症反应的肠道菌群及其产物将为阐明肠-肝轴对肝脏炎症发生、发展所起的作用奠定基础,为揭示非酒精性脂肪性肝病发生、发展的机制开辟新思路,为该病的防治探索新策略。     

炎症与抗炎

本文简介近二十年关于炎症与抗炎理论研究的进展。在机体受损伤时所出现的炎症是以局部反应为主的全身性反应,是机体的防御反应之一,可以将炎症分为血管通透性亢进、白细胞游走和增殖等三期。实验性炎症模型也有了不少较为深入的研究。引起炎症的主要化学介质有组织胺、5-羟色胺、激肽、激活的补体系统、溶酶体和前列腺素等。目前认为抗炎药物的作用原理是:甾体类稳定溶酶体膜,非甾体类抑制前列腺素的合成。许多方法可用于抗炎中药的研究。     

n-3脂肪酸代谢产物抗炎作用的研究进展

炎症反应是机体正常组织对感染和损伤的应答,然而过度的炎症反应往往会引起急性和慢性疾病的发生.最近研究发现,由n-3多不饱和脂肪酸二十碳五烯酸和二十二碳六烯酸代谢产生的resolvins和protectins两类化合物,具有很强的抗炎和炎症修复活性.综述了resolvins和protectin D1的来源、抗炎作用和抗炎机制,为进一步开展n-3多不饱和脂肪酸及其代谢产物的抗炎作用研究、为炎症的防治提供新的思路.     

NLRP6炎症小体与肠道微生态研究进展

NLRP6炎症小体作为炎症反应的核心识别环节,由PRRs、ASC、Caspase三部分组成,可激活下游IL-1β、IL-18等炎症分子.肠道微生态主要由肠道内结构复杂的微生物、种类繁多的代谢物和肠道黏膜屏障组成,参与机体多种重要生命功能,与多种疾病发生发展密切相关.NLRP6炎症小体广泛分布于肠道组织中,可识别肠道内多...     

脓毒症的负性调控机制

脓毒症是宿主对侵入性感染衍生的全身炎症反应,可能会导致感染性休克,多器官功能衰竭和死亡。机体在免疫应答正常或没有外界急性损害的情况下,正向与负向调控处于平衡状态,但脓毒症时机体不仅出现过度的炎症反应,还存在细胞因子减少,信号通路降低等现象,这与脓毒症的负向调控密切相关。本篇综述将系统总结在脓毒症的发生发展中所涉及到的负性调控机制,为脓毒症的治疗提供新的思路。     

Physicochemical and biological properties of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose (6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin)

A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The physicochemical and biological properties of (G(2))(3)-betaCD were determined together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha-cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)-betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of (G(2))(3)-betaCD were measured using various 2D NMR techniques. The solubility of (G(2))(3)-betaCD in water and MeOH-water solutions was extremely high in comparison with nonbranched betaCD and was about the same as that of the other monobranched betaCDs. The formation of an inclusion complex of (G(2))(3)-betaCD with stereoisomers (estradiol, retinoic acid, quinine, citral, and glycyrrhetinic acid) depends on the cis-trans isomers of guest compounds. The cis isomers of estradiol, retinoic acid, and glycyrrhetinic acid were included more than their trans isomers, while the trans isomers of citral and quinine fit more tightly than their cis isomers. (G(2))(3)-betaCD was the most effective host compound in the cis-trans resolution of glycyrrhetinic acid. Among the branched betaCDs, (G(2))(3)-betaCD exhibited the weakest hemolytic activity in human erythrocytes and showed negligible cytotoxicity in Caco-2 cells up to 200 microM. These results indicate unique characteristics of (G(2))(3)-betaCD in some biological responses of cultured cells.     

Conformational analysis of the tetranucleotides m6(2)A-m6(2)A-U-m6(2)A(m6(2)A = N6-dimethyladenosine) and U-m6(2)A-U-m6(2)A and of the hybrid dA-r(U-A). A one- and two-dimensional NMR study

A 1H-NMR investigation was carried out on the tetranucleotides U-m6(2)A-U-m6(2)A and m6(2)A-m6(2)A-U-m6(2)A (m6(2) = N6-dimethyladenosine) as well as on the hybrid trinucleotide dA-r(U-A). An extensive comparison with m6(2)A-U-m6(2)A and other relevant compounds is made. Previous proton NMR studies on trinucleotides have shown that purine-pyrimidine-purine sequences prefer to adopt a mixture of states which have as a common feature that the interior pyrimidine residue bulges out, whereas the flanking purine residues stack upon each other. A stacking interaction on the 3' side of the bulge is known to have no measurable effect on the bulge population. Chemical-shift data, ribose ring conformational analysis and information from NOE experiments now show unambiguously that the moderate U(1)-m6(2)A(2) stack in U-m6(2)A-U-m6(2)A diminishes the population of bulged-out structures in favour of a regular stack. This tendency towards conformational transmission in the downstream 5'----3' direction is fully confirmed by the fact that the strong m6(2)A(1)-m6(2)A(2) stack in the tetranucleotide m6(2)A-m6(2)A-U-m6(2)A virtually precludes the formation of bulged-out structures. The conformational characteristics of dA-r(U-A) appear comparable with those of m6(2)A-U-m6(2)A, which indicates that the presence of a 2'-hydroxyl group in the first purine residue is not a necessary prerequisite for the formation of a bulge.     

Characterization of O(6)-methylguanine-DNA-methyltransferase (O(6)-MGMT) activity in Xiphophorus fishes

We utilized a custom-synthesized double-strand oligonucleotide containing a single O(6)-methylguanine (O(6)-MG) residue within a restriction endonuclease recognition site to determine O(6)-methylguanine-DNA-methyltransferase (O(6)-MGMT) activity in various tissue extracts prepared from Xiphophorus fish. The results suggest Xiphophorus fish O(6)-MGMT activity has many of the same characteristics as Escherichia coli and mammalian O(6)-MGMT's including rapid reaction kinetics consistent with stoichiometric removal of methyl groups, but exhibits a temperature optimum of 23 degrees C.Results from protein extract activity assays indicate O(6)-MGMT activity patterns among four Xiphophorus tissues followed the order: brain> or =testes>gill> or =liver. In mammals, O(6)-MGMT activity is high in liver, while activity in brain is minimal (i.e. approximately 9% of liver); however, we report that in the Xiphophorus fishes examined, brain tissue extracts exhibited much higher (approximately six-fold) O(6)-MGMT activity levels than liver. Comparison of O(6)-MGMT activity between Xiphophorus species employed in tumor induction experiments did not indicate significant differences in ability to clear the pre-mutagenic O(6)-MG from the oligonucleotide substrate.     

6-Phosphogluconate Dehydrogenase (6PGD) Gene Duplication in Kalimeris (Asteraceae)

Abstract The genus Kalimeris with a diagnostic character of short or inconspicuous pappus consists of two sections, Asteromoea and Cordifolium. As a result of 6PGD isozyme analysis, sect, Asteromoea, including 2 × and poly-ploid taxa from 5 × to 8 ×, show similar cytosolic isozyme multiplicity and share a monomorphic locus. The data suggest that gene duplication of polyploid members was derived from a common ancestor. K. miqueliana, belonging to sect. Cordifolium. also possessed a gene duplication in 6PGD, though significant differences were detected in electrophoretic mobility between the sections. The occurrence of gene duplication in East Asian diploid Astereae leaves intact the validity of the allopolyploid-origin hypothesis of n= 9, which was rejected by Gottlieb (1981a) in American Astereae.     

Non-Microtubular Localizations of Microtubule-Associated Protein 6 (MAP6)

MAP6 proteins (MAP6s), which include MAP6-N (also called Stable Tubule Only Polypeptide, or STOP) and MAP6d1 (MAP6 domain-containing protein 1, also called STOP-Like protein 21 kD, or SL21), bind to and stabilize microtubules. MAP6 deletion in mice severely alters integrated brain functions and is associated with synaptic defects, suggesting that MAP6s may also have alternative cellular roles. MAP6s reportedly associate with the Golgi apparatus through palmitoylation of their N-terminal domain, and specific isoforms have been shown to bind actin. Here, we use heterologous systems to investigate several biochemical properties of MAP6 proteins. We demonstrate that the three N-terminal cysteines of MAP6d1 are palmitoylated by a subset of DHHC-type palmitoylating enzymes. Analysis of the subcellular localization of palmitoylated MAP6d1, including electron microscopic analysis, reveals possible localization to the Golgi and the plasma membrane but no association with the endoplasmic reticulum. Moreover, we observed localization of MAP6d1 to mitochondria, which requires the N-terminus of the protein but does not require palmitoylation. We show that endogenous MAP6d1 localized at mitochondria in mature mice neurons as well as at the outer membrane and in the intermembrane space of purified mouse mitochondria. Last, we found that MAP6d1 can multimerize via a microtubule-binding module. Interestingly, most of these properties of MAP6d1 are shared by MAP6-N. Together, these results describe several properties of MAP6 proteins, including their intercellular localization and multimerization activity, which may be relevant to neuronal differentiation and synaptic functions.     

X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons

Electrophoretic polymorphisms of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were examined in captive colonies of five subspecies of baboons (Papio hamadryas). Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism. Insufficient family data were available to confirm autosomal inheritance of the 6PGD polymorphism, but the electrophoretic patterns of variant types (putative heterozygotes) suggested the codominant expression of alleles at an autosomal locus. Implications of the G6PD polymorphism are discussed with regard to its utility as a marker system for research on X-chromosome inactivation during baboon development and for studies of clonal cell proliferation and/or cell selection during the development of atherosclerotic lesions in the baboon model.