Regulatory Effect of General Anesthetics on Activity of Potassium Channels / 神经科学通报·英文版

General anesthesia is an unconscious state induced by anesthetics for surgery. The molecular targets and cellular mechanisms of general anesthetics in the mammalian nervous system have been investigated during past decades. In recent years, K channels have been identified as important targets of both volatile and intravenous anesthetics. This review covers achievements that have been made both on the regulatory effect of general anesthetics on the activity of K channels and their underlying mechanisms. Advances in research on the modulation of K channels by general anesthetics are summarized and categorized according to four large K channel families based on their amino-acid sequence homology. In addition, research achievements on the roles of K channels in general anesthesia in vivo, especially with regard to studies using mice with K channel knockout, are particularly emphasized.

Exogenous hydrogen sulfide attenuates gastric ischemia-reperfusion injury via activation of K(ATP) channel / 生理学报

The present study aimed to investigate the protective effect and mechanism of hydrogen sulfide donor NaHS administration against gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) in rats. GI-R injury was induced by clamping the celiac artery of adult male SD rats for 30 min and followed by reperfusion for 1 h. The rats were randomly divided into sham group, GI-R group, NaHS group, glibenclamide group and pinacidil group. Gastric mucosal damage was analyzed with macroscopic injured area, deep damage was assessed with histopathology scores, and the hydrogen sulfide concentration in plasma was determined by colorimetric method. The results showed that pretreatment of NaHS significantly reduced the injured area and deep damage of the gastric mucosa induced by GI-R. However, NaHS did not significantly alter the levels of hydrogen sulfide in plasma 14 d after NaHS administration. The gastric protective effect of NaHS during reperfusion could be attenuated by glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker. However, K(ATP) opener pinacidil inhibited the GI-R-induced injury. These results suggest that exogenous hydrogen sulfide plays a protective role against GI-R injury in rats possibly through modulation of K(ATP) channel opening.

Bone marrow stromal cell line co-transfected with IL-2 and IL-3 genes can accelerate restoration of T-cell immunity in allo-BMT mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient. The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2 + IL-3 on the reconstitution of T-cell immunity in allo-BMT mice.</p><p><b>METHODS</b>The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system. T lymphocyte subset counts per spleen were analyzed by flow cytometry. Lymphocyte proliferation response to ConA was examined to evaluate T-cell function. CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation.</p><p><b>RESULTS</b>Gene engineered bone marrow stromal cell line QXMSC1-IL-2 + IL-3 could express IL-2 and IL-3 [1,300 ng.day(-1).10(-6) cells and 1100 ng.day(-1).10(-6) cells, respectively] under the control of doxycycline. QXMSC1-IL-2 + IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD(4)(+) and CD(8)(+) T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group (P < 0.01); make CD(4)(+)/CD(8)(+) ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA (P < 0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice (P < 0.05).</p><p><b>CONCLUSION</b>The gene transduced stromal cell line QXMSC1-IL-2 + IL-3 is able to accelerate T-cell immunity in allo-BMT mice.</p>

The improving effect of bone marrow stromal cell transfected with IL-3 gene on hematopoietic reconstitution in bone marrow transplantation of mice / 中国实验血液学杂志

To study the improving effect of regulatable gene of IL-3 engineered bone marrow stromal cell on the hematopoietic reconstitution in allogeneic bone marrow transplantation, an inducible gene expression system was established in a bone marrow stromal cell line which expressed IL-3 gene induced by doxycycline (Dox). The lethally irradiated mice C57BL/6 (H-2(d)) were co-transplanted with allogeneic bone marrow (BALB/c, H-2(d), 1 x 10(7)/mice) in which T cell were depleted by monoclonal antibody anti-Thy1.2 added with complement and the gene engineered stromal cell QXMSC1tet-on + IL-3 (5 x 10(5)/mice) at the same time. Dox was administrated continuously for 15 days to induce the expression of IL-3. The hematopoiesis in the bone marrow transplanted mice were observed at 30, 60 days post-transplantation, respectively. The numbers of RBC and WBC in peripheral blood were counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were measured in recipient bone marrow. The results showed that the engineered stromal cell line achieved high-level and controllable IL-3 expression. Co-graft with QXMSC1tet-on + IL-3 significantly increased the number of RBC, WBC in recipient peripheral blood, and the nucleated cells, CFU-S, CFU-GM, CFU-E, CFU-GEMM in bone marrow, compared with those coinfused with QXMSC1 or QXMSC1tet-on-TRE as control. In conclusion, regulatable gene IL-3 engineered bone marrow stromal cells accelerates hematopoietic reconstitution after allogeneic bone marrow transplantation.