Peripheral blood flows during colorectal distension in anaesthetised dogs

Distension of the descending colon elicits reflex cardiovascular responses, including increases in heart rate and arterial blood pressure. To study the relative contribution of vasoconstriction in individual vascular beds to this reflex response, experiments were performed on seven dogs anaesthetised with chloralose and instrumented with electromagnetic flowmeters around the superior mesenteric, the left renal and the left external iliac arteries. The colorectal portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa mean; range 25–50 mm Hg, 3.3–6.7 kPa) with warm Ringer solution for periods of 2 min. After a set of control distensions, the experiments were performed whilst the reflex rise in arterial pressure was prevented by removal of blood from the arterial tree. In control distensions arterial pressure increased by 11.3±1.5 mm Hg, 1.51±0.12 kPa (mean±SEM). In distensions at constant arterial pressure, peripheral blood flows were altered to different extents in the three territories studied: vascular resistance increased by 30.8±5.6% (P<0.01) in the mesenteric, by 4.1±1.5% (P<0.03) in the renal, and by 15.2±6.8% (NS) in the external iliac bed. We conclude that colorectal distension may reflect activation of a function-specific pathway of the sympathetic nervous system, which leads to much greater vasoconstriction in the splanchnic circulation than in renal or musculocutaneous circulations.     

The renal cell carcinoma lysis by a specific cytotoxic T cell clone is independent of the Fas/Fas-L cytotoxic pathway

The expression of Fas antigen at the surface of renal cell carcinoma and the susceptibility to Fas-mediated lysis by a tumor specific CTL clone were investigated. Renal cell carcinoma cell lines expressed Fas antigen and were susceptible to apoptosis mediated by antibodies to Fas/APO1. Using RT-PCR, we further showed that these cell lines expressed mRNA for Fas deleted transmembrane region, corresponding to a soluble form of Fas/APO-1. To investigate the role of the Fas/FasL pathway in the cytotoxic response against RCC cells, we analyzed the induction of Fas-L on a tumor specific T cell clone (CTL 8C2), previously generated against one RCC cell line. Fas-L expression on CTL 8C2 was detected by RT-PCR after stimulation with autologous tumor cells. However, the cytotoxic activity of CTL 8C2 was completely abolished when EGTA was added, suggesting that the cytolysis was mainly mediated by a Ca++-dependent pathway, perforin/granzyme-based.     

NM23基因相关信号通路在肿瘤转移中作用机制的研究进展

浸润和转移是恶性肿瘤的重要特征,也给肿瘤的治疗带来困难,是预后不良的重要因素.转移抑制因子23(non-metastasis,NM23)基因是最早发现的抗肿瘤转移基因之一.现在已经发现NM23是一个基因家族,包括NM23-H1、NM23-H2等重要的基因家族成员.研究表明NM23基因表达与实体瘤转移抑制有关,在很多实体瘤中可以作为进展和预后的分子标记.随着对NM23基因调控肿瘤转移的分子机制的研究的进一步开展,已经发现了一些NM23肿瘤转移抑制通路上下游的相关调控分子,为进一步的信号通路研究创造了条件.本文概述了近年来对NM23基因转移抑制通路研究的新近展,提出了以后可能的研究方向和需要解决的关键问题.     

紫草素通过PI3K/Akt通路抑制氧糖剥夺诱导的大鼠原代皮层神经元凋亡

目的:探讨紫草素对氧糖剥夺(OGD)损伤模型中大鼠原代皮层神经元的作用及机制。方法:用不同浓度(0. 02、0. 2、2和20μmol/L)紫草素对大鼠原代皮层神经元经进行预处理,再经OGD损伤处理,用乳酸脱氢酶(LDH)释放法和荧光素二乙酸酯/碘化丙啶(FDA/PI)双染法分别检测神经元活性和凋亡情况,选择最适紫草素浓度。然后,在加入紫草素之前提前加入LY294002(PI3K/Akt信号通路抑制剂,1μmol/L),用Wesern blot法检测神经元p-Akt(Ser473)水平变化,用LDH法和FDA/PI双染法检测神经元活性和凋亡率变化。结果:0. 2、2及20μmol/L的紫草素可显著提高神经元存活率(P 0. 05),同时还可使神经元内p-Akt(Ser473)水平显著升高(P 0. 05); LY294002可显著阻断紫草素对神经元p-Akt(Ser473)水平和凋亡率的影响(P 0. 05)。结论:紫草素可通过激活PI3K/Akt通路来减少OGD诱导的大鼠原代皮层神经元凋亡。     

NM23基因相关信号通路在肿瘤转移中作用机制的研究进展

浸润和转移是恶性肿瘤的重要特征,也给肿瘤的治疗带来困难,是预后不良的重要因素.转移抑制因子23(non-metastasis,NM23)基因是最早发现的抗肿瘤转移基因之一.现在已经发现NM23是一个基因家族,包括NM23-H1、NM23-H2等重要的基因家族成员.研究表明NM23基因表达与实体瘤转移抑制有关,在很多实体瘤中可以作为进展和预后的分子标记.随着对NM23基因调控肿瘤转移的分子机制的研究的进一步开展,已经发现了一些NM23肿瘤转移抑制通路上下游的相关调控分子,为进一步的信号通路研究创造了条件.本文概述了近年来对NM23基因转移抑制通路研究的新近展,提出了以后可能的研究方向和需要解决的关键问题.     

Age-related changes in the cerebrospinal fluid outflow glycosaminoglycans

The glycosaminoglycan distribution patterns of the cerebrospinal fluid (CSF) outflow pathway, dura mater and cerebral cortex of young New Zealand red rabbits and 1-, 3- and 12-week-old C-57 mice were identified by analyses of the glycosaminoglycan moieties and by the use of zone electrophoresis. The glycosaminoglycans were identified by specific degradation procedures, i.e., hyaluronate lyase, chondroitin ABC lyase, endo-gb-D-galactosidase and nitrous acid treatment. The CSF outflow pathway and dura mater glycosaminoglycan components were primarily hyaluronic acid and chondroitin sulfatedermatan sulfate, whereas the cerebral cortex glycosaminoglycan components were hyaluronic acid, chondroitin sulfatedermatan sulfate, keratan sulfate and heparan sulfate. The glycosaminoglycan components of the dura mater and cerebral cortex decreased and those of the CSF outflow pathway increased as a function of age. These results demonstrate the feasibility of analyses of the CSF outflow pathway glycosaminoglycan components and suggest that topographical changes in the glycosaminoglycan distribution profiles may contribute to the pattern of cerebrospinal fluid outflow.     

脑缺血后TLR4作用与小胶质细胞的激活

脑缺血性损伤早期小胶质细胞即被激活。激活的小胶质细胞既有细胞毒性又有神经营养作用。小胶质细胞行使免疫功能的信号转导受体之一是TLR4（toll-like receptor 4）。TLR4在脑内主要表达在小胶质细胞，是一种模式识别受体（pattern recognition receptor，PRR）, 识别一些外源性和内源性的配体。最近的研究表明，TLR4信号通路在脑缺血再灌注损伤中起重要作用。TLR4通过激活小胶质细胞，大量表达炎症因子，加重脑缺血性损伤。