Activation of peripheral 5-HT4 receptors attenuates colonic sensitivity to intraluminal distension

Tegaserod is a 5-HT(4) receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5-HT(4) receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0-60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid-induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1-10 mg kg(-1)) caused dose-dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5-HT(4) antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5-HT(4) receptors.     

七氟醚和缺氧预适应诱导乳鼠心肌细胞HSP70表达的改变

目的 :探讨七氟醚预适应和缺氧预适应对乳鼠心肌细胞热休克蛋白 70表达的影响。方法 :第 2代培养心肌细胞随机分为正常对照组 (C组 )、缺氧 /复氧组 (A/R组 )、缺氧预适应组 (IP组 )和七氟醚预适应组 (S组 ) ,每组均缺氧 2h ,复氧 48h。分别取复氧 0 ,1,12 ,2 4,36和 48h的细胞 ,用免疫组化染色检测HSP70 表达并进行图象分析。结果 :在各个时间点 ,S组和IP组间的HSP70 表达均显著高于A/R组和C组 (P <0 .0 1) ,A/R组的HSP70 表达略高于C组 ,S组和IP组间的HSP70 表达差异无显著性 (P >0 .0 5 )。随着复氧时间的延长 ,S组和IP组间的HSP70 表达从 1h开始增加 ,2 4h表达最强 ,与 1h相比差异具有显著性 (P <0 .0 5 )。结论 :七氟醚预处理和缺氧预处理均可诱导乳鼠心肌细胞HSP70 在延迟相呈高表达 ,提示HSP70 参与了七氟醚预适应和缺氧预适应的延迟保护相。     

成年大鼠纹状体海人藻酸损伤后nestin的表达

目的　 研究成年大鼠纹状体海人藻酸 (kainicacid,KA)损伤后不同时间点nestin的表达并探讨其机制。方法　向成年SD大鼠纹状体内立体定位注射 0 .5 μlKA(1mg/ml) ,分别于手术后第 1、3、7、14天用免疫组织化学法检测纹状体内nestin表达的变化。结果　 正常纹状体内可观察到微弱的淡染nestin样免疫活性阳性细胞 ;大鼠纹状体KA损伤后 1d ,nestin样免疫活性增强 ;第 3天nestin样免疫活性达峰值 ,nestin样免疫活性阳性细胞的胞体肥大 ,突起粗大 ,分支增加 ;此后nestin样免疫活性阳性细胞染色强度减弱 ,其胞体和突起逐渐变小变细。 结论　 成年大鼠纹状体内注射海人藻酸可诱导nestin的大量表达 ,该表达可能与脑损伤后的自身修复相关。     

头皮针对脑缺血模型大鼠血浆内皮素-1的影响

目的 :研究头皮针对脑缺血模型大鼠内皮素 - 1 ( ET- 1 )的影响 ,并与电针组比较。方法 :Wistar大鼠 5 0只 ,随机分正常、假手术、模型、电针、头皮针五组 ,每组 1 0只 ,后四组均于造模后 72小时、1 0天、1 5天取血测 ET- 1 ,并与手术后 6小时测定值进行比较 ;前三组不治疗 ,后两组造模后分别用电针与头皮针治疗。观察治疗前后 ET- 1测定值。结果 :神经功能评分 ,术后 1 0天与 1 5天 ,治疗组与模型组有显著性差异 ( P<0 .0 5～ 0 .0 1 ) ,电针组与头皮针组 ET- 1测定值无明显差异。对ET- 1的影响 ,术后 72小时及 1 0天时 ,治疗组 ET- 1明显低于模型组 ( P<0 .0 5 ) ,头皮针组明显低于电针组 ( P<0 .0 5 )。结论 :头皮针可在脑缺血早期就明显降低血浆 ET- 1含量 ,这可能是头皮针减轻脑缺血损伤并促进肢体功能恢复的机制之一。     

P-glycoprotein,multidrug resistance and tumor progression

P-glycoprotein (Pgp) is a plasma membrane protein that was first characterised in multidrug resistant cell lines. The occurrence of Pgp in clinical tumors has been widely studied. Recent investigations have begun to focus on the relationship between Pgp detection in tumors and treatment outcome. In several types of tumors, detection of Pgp correlates with poor response to chemotherapy and shorter survival. P-glycoprotein overexpression often occurs upon relapse from chemotherapy but may also occur at the time of diagnosis. Studies of experimental rat liver carcinogenesis have shown that Pgp expression increases in late stages of carcinogenesis, suggesting that Pgp may be involved in tumor progression. While some of the Pgp isoforms are known to transport hydrophobic chemotherapeutic drugs out of tumor cells, the biologic effects of Pgp overexpression in tumor cells are not fully understood, because the spectrum of substrates for Pgp-mediated transport has not been determined. In the rat liver carcinoma model, strong expression of Pgp is associated with a highly vascular stroma, suggesting that Pgp in tumor cells may affect the connective tissue stroma. The regulation of Pgp appears to be complex, and little is known about how it is up-regulated during carcinogenesis. Further studies of the role of Pgp in malignancy may contribute to our understanding of molecular mechanisms which underlie tumor progression.     

High-resolution imaging of progressive articular cartilage degeneration.

The objective of this study was to develop and verify a new technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 microm. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage.     

备用根大鼠脊髓后角提取液中神经营养活性组分的分离及生物活性测定

制作备用根大鼠脊髓后角提取液，取其分子量大于10kD的组分进行SDS-聚丙烯酰胺凝胶电泳分析，发现手术侧和非手术侧的电泳区带数目大致相同，但手术侧样品的第四条蛋白质区带扫描的吸收峰面积百分比大于非手术侧样品的第四条区带，两者在量上可能有差别。将手术侧样品经交联葡聚精G-75凝胶层析，得到两个洗脱峰．第一峰洗脱液有促进体外培养的背根节神经元存活及其突起生长的作用，其电泳分析显示4条主带，分子量在40～80kD之间．实验结果提示部分去传入纤维支配的脊髓后角组织含有神经营养活性物质，该物质的分子量约在40～78kD之间．     

电刺激大鼠下丘脑弓状核对中脑导水管周围灰质单位放电的影响

用玻璃微电极引导大鼠中脑导水管周围灰质（ＰＡＧ）单位放电。发现：电刺激弓状核（ＡＲＣ）后，在所观察的６４个ＰＡＧ单位中，表现为抑制的有３７个单位，其余单位分别表现为先抑制后兴奋、兴奋和无变化。结果表明，大鼠ＡＲＣ对ＰＡＧ单位活动的调制作用以抑制米。     

大鼠脊髓缺血再灌流时脊髓神经元对躯体和内脏传入刺激的反应

５０只大鼠用乌拉坦麻醉，箭毒制动。通过阻断腹主动脉血流以模拟腰段脊髓的局部缺血和再灌流损伤，玻璃微电极记录Ｌ２节段脊髓单位放电（ＳＣＵＤｓ），观察缺血再灌流时脊髓神经元对腓神经刺激（ＰＮＶ），内脏大神经刺激（ＶＬＮＶ）及两者同时刺激（ＳＶ）的反应。结果在缺血前所记录的１３３个自发放电单位中，对３种刺激均产生兴奋（Ｅ）、抑制（Ｉ）及无反应（ＮＲ）３种形式的反应，表明大鼠Ｌ２节段脊髓存在躯体、内脏和躯体内脏反应性神经元，并有会聚和阻塞现象。在脊髓缺血再灌流时，神经元对ＰＮＶ、ＶＬＮＶ、ＳＶ也产生Ｅ、Ｉ、ＮＲ３种形式的反应，提示脊髓缺血再灌流时神经元对躯体和内脏传入刺激的反应形式不受影响；但缺血时ＳＣＵＤｓ对ＰＮＶ、ＶＬＮＶ产生反应的单位数减少，这表明脊髓缺血损伤时神经元对躯体和内脏传入刺激的反应性减弱，随着缺血损伤加重，脊髓神经元对躯体内脏信号的整合功能下降