五子降糖方对T2DM大鼠血糖、C-P及DPP-4活性影响的实验研究

[目的]探讨五子降糖方对二肽基肽酶Ⅳ(DPP-4)活性的影响,研究其发挥降糖作用的可能机制。[方法]选取SPF级雄性GK大鼠,适应性喂养1周后给予高脂饲料,连续喂养4周,测定血糖,以随机血糖11.1 mmol/L或餐后2 h血糖(2 h PG)16.7 mmol/L为成模标准,将成模2型糖尿病(T2DM)大鼠随机分为模型组、二甲双胍组(0.1 g/kg)、五子降糖方低、中、高剂量组(3.5、7.0、14 g/kg,折合生药量),同时另选Wstar大鼠为正常组,正常组与模型组灌胃等体积纯净水,灌胃前测定空腹血糖(FBG),灌胃后4周、8周测定FBG及2 h PG,8周后处死动物,检测血清C肽(CP)水平;采用发色底物法建立DPP-4抑制剂体外筛选模型,分别应用五子降糖方及其组方的各味单药菟丝子、女贞子、紫苏子、莱菔子、车前子水提物对DPP-4抑制剂体外筛选模型进行干预,以磷酸西格列汀片作为阳性对照药,测定A值,计算DPP-4抑制率,比较IC50差异。[结果]五子降糖方可降低T2DM大鼠FBG及2 h PG,增高血清C-P水平;对DPP-4抑制作用,五子降糖方IC50为(6 667.754±2 119.759)mg/L,其组成药物中莱菔子IC50为(382.554±7.750)mg/L,菟丝子IC50为(843.391±135.230)mg/L。[结论]五子降糖方可以降低T2DM FBG及2 h PG,改善胰岛β细胞功能,作用机制可能与DPP-4抑制作用有关,其中莱菔子、菟丝子可能是本方发挥DPP-4抑制作用的主要药物。     

地格达-4味汤中獐牙菜苦苷在急性肝损伤模型大鼠体内药代动力学研究

目的:建立急性肝损伤模型大鼠血清中獐牙菜苦苷的HPLC血药浓度测定方法,并对其药代动力学进行研究.方法:SD大鼠腹腔注射D-半乳糖胺(D-GIaN) (400 mg·kg-1),制备急性肝损伤模型,按高、中、低(0.39,0.77,1.54 g·kg-1)剂量灌胃给予地格达-4味汤,收集不同时间点含药血清,HPLC测定血药浓度,采用Winnonlin 5.1药动学软件拟合房室模型,计算其药动学参数.结果:獐牙菜苦苷在0.000 6 ～0.019 2 mg ·L-1(r =0.998 9)线性关系良好,平均回收率均在80％以上,方法学考察其他项均符合实验要求.地格达-4味汤高、中、低剂量组吸收半衰期基本一致,药时曲线下面积(AUC)与给药剂量之间呈现良好的线性关系,属于线性动力学过程.结论:獐牙菜苦苷在急性肝损伤模型大鼠体内的药时曲线符合二室模型特征;所建立的方法准确,灵敏度高,专属性好,可作为獐牙菜苦苷体内血清药物浓度分析方法.     

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.     

Granuloma annulare-like eruption due to chronic Epstein-Barr virus infection

A 32-year-old woman afflicted with a severe, chronic Epstein-Barr virus (CEBV) infection of 12 months' duration developed an unusual, granuloma annulare-like eruption. The cutaneous disorder, which paralleled the clinical course of her disease, was characterized by slightly raised, erythematous, annular lesions predominantly involving the face and arms, with sporadic involvement elsewhere. Histopathologic examination of biopsy material obtained from affected skin disclosed a granulomatous dermatitis. The patient's symptoms and cutaneous eruption resolved after systemic corticosteroid therapy. This eruption may represent a distinct cutaneous component of CEBV infection with clinically granuloma annulare-like features or the mere serendipitous association of CEBV infection and an unusual granulomatous dermatitis. Because of the unusual clinical appearance of the eruption and its clear correlation with disease activity, we speculate that it likely represents a distinct cutaneous condition, heretofore unreported, caused by CEBV infection.     

几种表面活性剂对P-gp底物罗丹明123经肠黏膜透过性的影响

 目的观察低浓度表面活性剂聚氧乙烯蓖麻油,Labrasol和聚山梨酯80对肠黏膜P-gp的调控作用。方法使用体外扩散池法评价罗丹明123(R123)经空肠、回肠和结肠黏膜的经时经吸收方向和分泌方向的透过量和透过系数(P_app),并测定不同浓度表面活性剂对R123和荧光素钠(CF)经肠黏膜透过性的影响。R123和CF在接受室中的浓度用荧光分光光度法测定。结果R123经肠道黏膜的透过性存在部位差,即以空肠、回肠和结肠的次序透过性依次减少。另一方面,R123经肠道分泌方向的透过性显著地高于其吸收方向的透过性。低浓度的CEL和Labrasol可显著增强R123经吸收方向的透过性,减少经分泌方向的透过性;而低浓度的聚山梨酯80可显著增强R123经吸收方向的透过性,但对经分泌方向的透过性无显著影响。但实验浓度的表面活性剂对CF的肠道转运没有影响。结论低浓度的聚氧乙烯蓖麻油、Labrasol和聚山梨酯80可通过对P-gp功能的抑制而用于改善受P-gp介导药物的吸收,有望提高此类药物的口服生物利用度。     

Global vascular expression of murine CD34, a sialomucin-like endothelial ligand for L-selectin

Extravasation of leukocytes into organized lymphoid tissues and into sites of inflammation is critical to immune surveillance. Leukocyte migration to peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and Peyer's patches (PP) depends on L-selectin, which recognizes carbohydrate-bearing, sialomucin-like endothelial cell surface glycoproteins. Two of these ligands have been identified at the molecular level. One is the potentially soluble mucin, GlyCAM 1, which is almost exclusively produced by high endothelial venules (HEV) of PLN and MLN. The second HEV ligand for L-selectin is the membrane-bound sialomucin CD34. Historically, this molecule has been successfully used to purify human pluripotent bone marrow stem cells, and limited data suggest that human CD34 is present on the vascular endothelium of several organs. Here we describe a comprehensive analysis of the vascular expression of CD34 in murine tissues using a highly specific antimurine CD34 polyclonal antibody. CD34 was detected on vessels in all organs examined and was expressed during pancreatic and skin inflammatory episodes. A subset of HEV-like vessels in the inflamed pancreas of nonobese diabetic (NOD) mice are positive for both CD34 and GlyCAM 1, and bind to an L-selectin/immunoglobulin G (IgG) chimeric probe. Finally, we found that CD34 is present on vessels of deafferentiated PLN, despite the fact that these vessels are no longer able to interact with L-selectin or support lymphocyte binding in vitro or trafficking in vivo. Our data suggest that the regulation of posttranslational carbohydrate modifications of CD34 is critical in determining its capability to act as an L-selectin ligand. Based on its ubiquitous expression, we propose that an appropriately glycosylated form of vascular CD34 may act as a ligand for L-selectin-mediated leukocyte trafficking to both lymphoid and nonlymphoid sites.     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971