慢性肝病蛋白C系统的变化及临床意义

目的：探讨血浆血栓调节蛋白（TM）、蛋白C（PC）和蛋白S（PS）与慢性肝病的关系。方法：用双抗体夹心ELISA法测定了136例慢性乙型肝炎和74例肝炎肝硬化患者血浆TM、PC和PS水平，并与35名正常者进行对照分析。结果：（1）慢性乙型肝炎及肝炎肝硬化患者血浆TM水平均显著增高。（2）慢性乙型肝炎及肝炎肝硬化患者血浆PC、PS水平均显著降低，并与病情严重程度呈显著负相关。结论：慢性乙型肝炎及肝炎肝硬化患者均存在肝窦内皮细胞损伤，且与凝血机制异常有关；检测血浆PC和PS可做为判断慢性肝病病情严重程度的指标。     

血浆蛋白C、蛋白S与脑梗死的相关性研究

目的研究血浆蛋白C、蛋白S与脑梗死发病的关系。方法对64例脑梗死患者及15例正常对照组进行血浆蛋白C(PC)、蛋白S(PS)检测,并分析其与脑梗死严重程度、年龄及其它脑梗死危险因素之间的关系。结果实验组血浆PC浓度(4.97±1.82μg/ml)与对照组血浆PC浓度(4.74±1.95μg/ml)之间差别无统计学意义;首发组血浆PC浓度(5.28±1.85μg/ml)与复发组血浆PC浓度(4.03±1.40μg/ml)之间差别有统计学意义(P=0.016);实验组血浆PS浓度(7.47±3.87μg/ml)与对照组血浆PS浓度(12.06±3.99μg/ml)之间差别有统计学意义,中老年组血浆PS浓度(6.58±3.33μg/ml)与青年组血浆PS浓度(9.28±4.33μg/ml)之间差别有统计学意义。结论PC降低是复发性脑梗死的危险因素之一;游离PS降低是脑梗死的危险因素;PS水平的降低导致PC功能的降低,进而凝血功能障碍,导致脑梗死的发生。     

Role of cytochrome P4502E1 in alcoholic liver disease pathogenesis

The intragastric tube feeding model is ideal for the study of the role of dietary factors and the effect of drugs on experimental alcoholic liver disease (ALD), since the model allows us to study the effect of a single variable in the diet on the pathology of liver where the blood alcohol level (BAL) is maintained over 150 mg%. By varying the dietary fatty acid composition we showed that the pathology was worsened by increasing linoleic acid or polyunsaturated fatty acids (PUFAs) in the diet where cytochrome P4502E1 (CYP2E1) was increased posttranslationally by high BAL. Concomitant with the increase in CYP2E1 there was evidence for an increase in lipid peroxidation (LP) by microsomes. Protein adducts of the products of LP were increased in the blood. Isoniazid (INH) enhanced this process and the pathology of ALD when INH was fed at therapeutic levels with ethanol. Preliminary studies show that diallyl sulfide, which inhibits and destroys liver CYP2E1 selectively, also modified the pathologic effects of ethanol. Thus we postulate that CYP2E1 induction plays a central role in the pathogenesis of ALD.     

Amadori糖化白蛋白对牛视网膜血管二酯酰甘油--蛋白激酶C级联的影响

目的 :探讨Amadori糖化血清白蛋白对牛视网膜血管二酯酰甘油 (DAG)———蛋白激酶C(PKC)信号级联的影响及d-α-生育酚的干预作用。方法 :体外制备的Amadori糖化的牛血清白蛋白 (AGSA)分别在生理浓度葡萄糖 (5 .5mmol/L)和高浓度葡萄糖 (2 0mmol/L)培养液中作用于新鲜牛视网膜血管。采用薄层层析和放射自显影法测定DAG含量和PKC活性 ;并检测d -α-生育酚预处理后DAG、PKC改变。结果 :在生理葡萄糖浓度下 ,牛视网膜血管暴露于AGSA2 4h或 72h后细胞内DAG含量、PKC活性均较对照组显著增加 ,当AGSA和高葡萄糖同时作用于牛视网膜血管时 ,DAG -PKC级联显著激活 ,分别为正常葡萄糖组的 3.4 7倍和 4 .5 4倍 ;在正常血清培养液中 ,与 5 .5mmol/L的葡萄糖相比 ,2 0mmol/L高糖在 2 4h时并不刺激DAG含量增加 (P >0 .0 5 ) ,而 72h时则较对照组增加 4 5 % ,PKC活性较对照增加 5 6 % ,而d -α -生育酚可逆转上述生化改变。结论 :Amadori糖化血清白蛋白可在生理葡萄糖浓度下刺激DAG -PKC途径活化 ,从而影响血管一系列生理功能 ,而d -α-生育酚对血管生化改变有保护作用。     

Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

CD117阳性小肠间质瘤中Ki67和p53蛋白的表达及在预后中的意义

目的 :研究小肠间质瘤 (smallbowelstromaltumors,SBST)Ki6 7和p5 3免疫组织化学的表达 ,探讨两者在肿瘤良恶性划分和预后中的作用。方法 :选用CD117阳性的SBST 33例进行光镜观察 ,用EnVisionTM+二步法免疫组化方法检测Ki6 7和 p5 3蛋白在肿瘤中的表达情况并与形态学进行比较。 结果 :33例SBST患者 ,男 2 0例 ,女13例 ,年龄 2 1～ 71岁 ,发生于十二指肠 5例 ,空肠 2 2例 ,回肠 6例。肿瘤最大径的范围在 1.5～ 2 0cm之间。在光镜下出现肿瘤内坏死的有 11例。肿瘤核分裂象计数每 5 0个高倍镜视野 0个有 6例 ,1～ 2个 5例 ,≥ 3个的有 2 2例。 33例中良性 4例 ,交界性 4例 ,恶性 2 5例。随访时间为 3～ 180个月 (平均 73.3个月 ) ,结果为良性组 4例均无瘤生存 ;交界性组 2例无瘤生存 ,1例失访 ,1例在无瘤生存 18个月后失访 ;恶性组无瘤生存有 7例 ,带瘤生存者及死亡有 16例 ,2例失访。Ki6 7染色阴性 2例 ,均为良性 ;其余 31例阳性中 ,增殖指数 (阳性细胞数 )大于 5 %的有恶性 16例 (94 .1% ) ,交界性 1例。在免疫组化p5 3染色中 ,恶性组 2 5例均呈阳性表达 (平均阳性细胞数 4 2 .9% ) ,其中 12例阳性细胞数大于 5 0 %。当Ki6 7和 p5 3均为阴性或两者阳性细胞数分别是 <1%和 <10 %时 ,肿瘤呈良性经过 ,预后     

胃肠道肿瘤病人围手术期细胞因子及蛋白质代谢的变化

目的 :探讨胃肠道肿瘤病人手术后肿瘤坏死因子 α (TNF α)、白介素 6 (IL 6 )、白介素 10 (IL 10 )的变化以及与蛋白质代谢的关系。　方法 :用酶联免疫法 (ELISA)检测 19例胃肠道肿瘤根治术病人术前和术后 1、3、5天血清TNF α、IL 6和IL 10水平 ,同时检测蛋白质分解代谢相关指标、2 4h尿中尿素和肌酐排泄量。　结果 :胃肠道肿瘤根治术后病人TNF α呈下降趋势 ,术后第 1天较术前明显下降 (P <0 .0 5 )。IL 6和IL 10术后升高 (P <0 .0 1) ,尤以术后第 1天升高明显。术后 2 4h尿中尿素和肌酐排泄量明显升高。　结论 :胃肠道肿瘤根治术后病人IL 6和IL 10的升高支持手术应激导致的细胞因子释放变化 ,但TNF α呈下降趋势 ,可能与胃肠道肿瘤病人术前TNF α的高表达有关。术后蛋白质分解代谢增加 ,可能与细胞因子IL 6和IL 10的升高有关。     

Glucocorticoid regulation of eicosanoid production by glial cells under basal and stimulated conditions

We measured the production of two eicosanoids, prostaglandin E₂ and thromboxane-B₂, by rat glial cell cultures under basal conditions, following stimulation with phorbol-12-myristate-13-acetate and the bacterial endotoxin lipopolysaccharide, and following treatment with synthetic glucocorticoids. Stimulation of rat glial cells in culture with either phorbol-12-myristate-13-acetate or lipopolysaccharide caused a 1.5–5.0-fold increase in prostaglandin E₂ production, but did not affect thromboxane production. Pretreatment of the cultures with dexamethasone markedly inhibited the stimulated production of prostaglandin E₂ but had only a modest effect on basal production. Dexamethasone did not affect the activity of the enzyme protein kinase C, a putative regulator of eicosanoid synthesis. Our findings show that glucocorticoids have the potential to modulate central nervous system eicosanoid production particularly under conditions of stimulated production, such as inflammatory and demyelinating disorders. This mechanism may explain, at least in part, the therapeutic benefit of glucocorticoids in patients with multiple sclerosis.     

Fentanyl and the interleukin-6 response to surgery

It has been suggested that large doses of opioids may suppress the interleukin-6 response to surgery. We examined the effects of the supplementation of inhalational anaesthesia with either 3 or 15 μg.kg⁻¹ fentanyl on the circulating interleukin-6, interleukin-8, C-reactive protein, cortisol and glucose concentrations in 16 patients undergoing pelvic surgery. In both groups, surgery evoked the expected glucose, cortisol and interleukin-6 response but no increase in interleukin-8 was detected. There were no significant differences between the two groups. We conclude that the supplementation of inhalational anaesthesia with conventional doses of opioids does not modify the cytokine response to surgery.