干扰素α干预对大鼠胰腺纤维化的影响

目的 观察干扰素α(INF-α)对DDC诱导的胰腺纤维化大鼠模型纤维增生程度、胰腺星状细胞活化标志物α-平滑肌肌动蛋白(α-SMA)和细胞外基质成分Ⅲ型胶原蛋白表达的影响.方法 Wistar大鼠40只随机数字法分成对照组、纤维化组和干扰素组.纤维化组和干扰素组每周2次腹腔内注射DDC,干扰素组在造模同时每天皮下注射INF-α10万U.6周末取材,光镜下观察胰腺病理学变化.免疫组化法测定胰腺组织中α-SMA、Ⅲ型胶原蛋白的表达.结果 第4周起纤维化组大鼠体重增长缓慢甚至下降,干扰素组体重仍缓慢增长,5周后两组差异显著[(309.8±19.7)g与(277.3±19.9)g,P＜0.05].纤维化组胰腺组织纤维化表现明显,纤维化分值、Masson染色值、α-SMA和Ⅲ型胶原蛋白相对表达量分别为2.679±0.899、218.713±36.102、148.971±30.686和88.142±42.581;干扰素组纤维化减轻,上述指标分别为1.952±0.219、114.732±24.912、77.237±9.275和59.952±25.498,均较纤维化组显著降低(P＜0.05).结论 给予INF-α能显著减轻纤维化程度和α-SMA、Ⅲ型胶原表达,对DDC诱导的大鼠胰腺纤维化有一定的预防作用.     

糖耐量减低与心血管疾病及阿卡波糖作用

Impaired glucose tolerance(IGT) is a clinical state between normal and abnormal glucose metabolism with increased risk of cardiovascular disease. Its mechanism mainly related to insulin resistance, oxidative stress ,blood hypercoagulability, inflammatory response ,as well as related lipotoxieity. α-glucosidase inhibitor acarbose is safe and effective to reduce postprandial hyperglycemia, and has been approved for the treatment of patients with IGT. A growing number of studies have shown that acarbose also has cardiovascular benefit.     

小儿脑性瘫痪脑血流动力学的研究

目的研究小儿脑性瘫痪(脑瘫)脑血流动力学的变化规律.方法应用经颅多普勒超声对347例脑瘫患儿与30例正常健康儿脑血流动力学参数进行对照检测.结果脑瘫患儿的大脑前动脉、大脑中动脉、大脑后动脉的平均血流较同年龄段的正常小儿显著下降(P＜0.05),而脑血管阻力指数则显著增高(P＜0.05).小于1岁年龄组的平均流速下降及脑血管阻力指数增高较其他年龄组更显著(P＜0.05).结论脑瘫患儿存在脑血流动力学的高阻力、低灌注障碍,早期应用改善脑微循环治疗对于小儿脑瘫的治疗有重要意义.     

An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice

Hepatocellular carcinoma (HCC) displays a high resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. To increase sensitivity of HCC cells to TRAIL, we have constructed an oncolytic adenoviral vector (ZD55) and used this vector to deliver second mitochondria-derived activator of caspases (Smac) and TRAIL genes (ZD55-Smac and ZD55-TRAIL, respectively) into HCC cells. Our data showed that human HCC cells express high levels of inhibitor of apoptosis proteins (IAPs). Transfected HCC cells expressing exogenous X-linked IAPs (XIAPs) displayed more resistance to TRAIL. The expression of Smac led to rapid and potent activation of apoptosis in HCC cells after infection with ZD55-Smac. The activation of caspases and induction of apoptosis could be enhanced further through coinfection with ZD55-TRAIL. The combined treatment of ZD55-Smac and ZD55-TRAIL resulted in significant reduction of XIAP expression levels. In addition, our in vivo data in mice showed only a partial response in the established tumor treated either by ZD55-Smac or ZD55-TRAIL alone. By contrast, complete tumor regression was observed by combination of ZD55-Smac and ZD55-TRAIL in all treated animals. This strong antitumoral activity achieved by this combination was due to a dramatic induction of tumor cell apoptosis in the treated tumors. In conclusion, our data indicate that Smac antagonizes the IAPs in HCC tumor cells and enhances tumor cell death induced by TRAIL in the oncolytic adenoviral vector. The combination of Smac and TRAIL delivered by way of the oncolytic adenoviral vector would provide a useful strategy for therapy of HCC and might also be applied to other IAPs abundant in cancers.     

Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells

AIM: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B. METHODS: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis. RESULTS: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change. CONCLUSION: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.     

慢性重型肝炎患者血清肝细胞生长因子浓度变化的动态观察

研究慢性病毒性肝炎患者血清中肝细胞生长因子(HGF)的浓度变化与病情的关系,用ELISA法检测19例慢性乙型重型肝炎患者(慢重肝)血清中的HGF浓度的动态变化,并比较生存患者和死亡患者的HGF变化,结果:1.慢重肝患者血清HGF浓度变化与血清TBil的变化相一致,生存患者HGF在达到一个峰值后随血清TBil的降低而降低;死亡患者的HGF则进行性升高,在死亡前达最高值。2.生存患者的HGF峰值浓度为(5.214±1.657)μg/L,TBil为(236±109)μmol/L,PTA为(48.26±10.15)％;而死亡患者分别为(7.521±2.152)μg/L、(412±128).μmol/L、(30.09±14.28)％,均有显著性的差异。HGF在慢重肝患者血清中有较明显的升高,而且与TBil的变化有相关性,动态观察血清HGF的变化可作为判断病情的指标之一。     

上海市不同人群人芽囊原虫感染调查

目的了解上海市不同人群人芽囊原虫感染情况。方法在上海市6个区收集居民新鲜粪便,采用Ringer溶液37℃恒温条件下培养人芽囊原虫,计算人芽囊原虫感染率。结果检查居民2 984人,人芽囊原虫阳性者88人,感染率2.95%。上海市各区人群感染率间差异无统计学意义(χ~2=9.90,P>0.05);青浦区男性感染率为5.56%,女性感染率1.57%,差异有统计学意义(χ~2=5.38,P<0.05),其他5个区男、女性感染率差异无统计学意义(χ~2=0.08～0.54,P均>0.05);农民感染率为6.87%,与其他职业人群比较差异有统计学意义(χ~2=18.57,P<0.05)。结论上海市人群对人芽囊原虫普遍易感,以农民感染率最高。体外培养法敏感性较高.可用于人芽囊原虫感染的流行病学调查。     

Effect of cardiac output reduction on rate of desaturation in obstructive apnea.

The nadir of SaO2 during an obstructive apnea is dependent upon the apnea's duration and the rate of fall of saturation (dSaO2/dt). We postulated that a low Q, such as in patients with congestive heart failure with sleep apnea, or a reduction in Q, as seen in some humans during obstructive sleep apnea, might steepen dSaO2/dt. The mechanism postulated was lowering of SvO2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen. This study examines dSaO2/dt following the onset of apnea in eight spontaneously breathing adult baboons. Nonrepetitive obstructive apneas (30, 45, and 60 seconds) were created by clamping an indwelling cuffed endotracheal tube at the end of expiration. Following baseline measurements, the animals were given a bolus of a rapid-acting beta-adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia. Fiberoptic catheters were used for continuous monitoring of SaO2, SvO2, and cardiac output. Esophageal pressure and relative thoracic gas volume (Respitrace) were monitored to insure equivalence of lung volume at the onset of apnea. Beta-adrenergic blockade reduced resting Q by a mean of 25 percent. The blocked vs unblocked dSaO2/dt was 0.73 vs 0.72 percent/s, 0.76 vs 0.73 percent/s, and 0.70 vs 0.71 percent/s for 30-second, 45-second, and 60-second apneas, respectively. Thus, mean dSaO2/dt for all durations of apneas was unaffected by beta-adrenergic blockade. We concluded that dSaO2/dt is not influenced by limited Q preceding or induced by obstructive asphyxia.