延迟性和痕迹性条件反射建立过程中豚鼠眨眼反应特征参数的变化

目的研究延迟性和痕迹性条件反射建立过程中豚鼠眨眼反应特征参数的变化。方法采用500 ms正弦波纯音和100 ms束状氧气流的配对刺激,训练豚鼠建立延迟性和痕迹性眨眼条件反射。在此过程中,使用张力换能器记录豚鼠左侧眼轮匝肌活动,并使用我室编制的Matlab软件分析眨眼行为数据。结果2组豚鼠均分别能建立延迟性和痕迹性眨眼条件反射。但是,相对于痕迹性条件反射训练组,延迟性条件反射训练组豚鼠表现出了更快的条件眨眼反应习得率和更高的条件眨眼反应峰幅度(P<0.01)。2组豚鼠条件眨眼反应峰潜伏期以及非条件眨眼反应的峰幅度和峰潜伏期在10 d条件反射训练过程中变化均不显著(P>0.05)。结论在2类条件反射训练过程中,豚鼠眨眼反应特征参数的变化规律与其他常用啮齿类动物模型相类似。     

盐酸布替萘芬乳膏的离体透皮吸收研究

目的:研究盐酸布替萘芬乳膏对离体豚鼠皮的透皮吸收情况,并对自制乳膏与国内外已上市产品的离体透皮渗透量进行比较。方法:采用透皮吸收仪,皮片涂药后不同时间采样,用高效液相色谱法测定样品中盐酸布替萘芬的浓度。结果:在50%乙醇生理盐水释放液中,国外产品、国内产品和自制产品36 h透皮渗透量分别只有0.061 89,4.661,和0.289 7μg.cm-2,盐酸布替萘芬乳膏透皮渗透量很低,三者无显著性差异。结论:自制盐酸布替萘芬乳膏的豚鼠离体透皮吸收程度与国外同类品种相当。盐酸布替萘芬乳膏主成分大部分滞留在皮肤,只有极少数透过皮肤屏障,有利于其发挥局部治疗作用。     

野百合碱诱导的肺动脉高压小型猪的肺病理改变

目的观察野百合碱诱导小型猪肺动脉高压模型不同时期心肺组织的病理变化。方法 12头雄性西藏小型猪,4.0~4.5月龄,体质量15.0~18.0 kg。测定12头小型猪平均肺动脉压作为基础值;然后选择10头小型猪腹腔注射野百合碱(MCT)10.0 mg/kg;给药4周和8周后再分别测定小型猪平均肺动脉压。分别于4、8周处死两头小型猪,采样观察小型猪心肺组织病理改变情况。结果给药4周和8周后,西藏小型猪的肺动脉压力与人体相近,正常平均肺动脉压约为(15.19±0.70)mmHg(1 mmHg=0.133 kPa);给药4周后平均肺动脉压升至(19.69±2.47)mmHg;给药8周后升至(25.62±4.88)mmHg,与基础压相比均有显著差异(P<0.01)。组织病理学分析显示,给药4周后即可形成有意义的病理改变,右心室肥厚;8周后有明显的病理学改变,如右心室纤维化和肺动脉中层增厚。结论 MCT给药8周后,造成肺动脉压力升高和肺血管重构,可以诱导西藏小型猪形成慢性肺动脉高压模型。     

不同眼轮匝肌活动记录方法对豚鼠痕迹性眨眼条件反射建立的影响

目的 比较不同眼轮匝肌活动记录方法 对豚鼠痕迹性眨眼条件反射建立的影响.方法 采用350 ms正弦波纯音和100 ms束状氧气流的配对刺激,训练豚鼠建立痕迹性眨眼条件反射.在此过程中,分别使用张力换能器和金属微电极记录眼轮匝肌活动,并使用我室编制的Matlab软件分析眨眼行为数据.结果 2种记录方法 条件下,豚鼠均能建立痕迹性眨眼条件反射,但应变片组动物条件眨眼反应的习得速率相对于肌电图组更快(P<0.05).此外,条件反射训练第10天,应变片组动物条件反应峰潜伏期显著迟于肌电图组(P<0.05).结论 相对于肌电图记录法,应变片记录法是一种更适合于豚鼠联想型学习神经生物学机制研究的记录方法 .     

Long‐Term Controlled Normoglycemia in Diabetic Non‐Human Primates After Transplantation with hCD46 Transgenic Porcine Islets

Xenotransplantation of porcine islets into diabetic non‐human primates is characterized by (i) an initial massive graft loss possibly due to the instant blood‐mediated inflammatory reaction and (ii) the requirement of intensive, clinically unfriendly immunosuppressive therapy. We investigated whether the transgenic expression of a human complement‐regulatory protein (hCD46) on porcine islets would improve the outcome of islet xenotransplantation in streptozotocin‐induced diabetic Cynomolgus monkeys. Immunosuppression consisted of thymoglobulin, anti‐CD154 mAb for costimulation blockade, and mycophenolate mofetil. Following the transplantation of islets from wild‐type pigs (n = 2) or from 1,3‐galactosyltransferase gene‐knockout pigs (n = 2), islets survived for a maximum of only 46 days, as evidenced by return to hyperglycemia and the need for exogenous insulin therapy. The transplantation of islets from hCD46 pigs resulted in graft survival and insulin‐independent normoglycemia in four of five monkeys for the 3 months follow‐up of the experiment. One normalized recipient, selected at random, was followed for >12 months. Inhibition of complement activation by the expression of hCD46 on the pig islets did not substantially reduce the initial loss of islet mass, rather was effective in limiting antibody‐mediated rejection. This resulted in a reduced need for immunosuppression to preserve a sufficient islet mass to maintain normoglycemia long‐term.     

哌仑西平促进豚鼠巩膜成纤维细胞分泌胶原及增殖的细胞内信号转导机制

目的探讨哌仑西平促进豚鼠巩膜成纤维细胞（GSF）分泌胶原及增殖的细胞内信号转导机制。方法体外培养GSF,采用免疫细胞化学染色法及羟脯氨酸测定法分别观察不同浓度哌仑西平溶液（1％、2％、3％、5％）作用下,GSF中Smad3、CTGF、Ⅰ型胶原表达量的变化和GSF培养上清中胶原含量的变化。结果在1％、2％、3％、5％浓度的哌仑西平溶液作用下,GSF中Smad3、CTGF、Ⅰ型胶原表达量明显增强;GSF培养上清中胶原含量均较对照组明显增加。哌仑西平的最小有效质量浓度是1％,在1％-5％浓度范围内,哌仑西平可促进GSF中Smad3、CTGF、Ⅰ型胶原表达量增强,3％哌仑西平溶液的促增强作用最强,但与5％的哌仑西平无显著差别。结论哌仑西平具有促进GSF分泌胶原和增殖的作用,其作用可能是通过smad3-CTGF信号转导通路实现的。     

Does the pre‐ischaemic administration of sevoflurane reduce myocardial stunning? A porcine experimental model

BACKGROUND: In a porcine model, the cardioprotective effect of sevoflurane was studied with regard to the preservation of myocardial contractility (myocardial stunning) after a myocardial ischaemic insult. METHODS: Twenty-seven pigs were randomized to receive either a dual 4% sevoflurane inhalation period as a supplement to pentobarbital anaesthesia or pentobarbital anaesthesia only before a 15-min ischaemic insult on the left anterior descending coronary artery. The ischaemic period was followed by 180 min of reperfusion. Myocardial contractility was assessed by myocardial sonomicrometry. RESULTS: A significant difference was found between the sevoflurane group and the control group at 5 min of reperfusion. However, subsequently, there was no overall difference between the two groups. CONCLUSION: Sevoflurane administered as a pre-ischaemic bolus does not provide long-term improvement of the myocardial contractility. However, it can be speculated that sevoflurane may induce an early improvement in contractility.     

The thalamic nucleus submedius and ventrolateral orbital cortex are involved in nociceptive modulation: A novel pain modulation pathway

Recently, a series of studies have given rise to and provided evidence for the hypothesis that the nucleus submedius (Sm) in the medial thalamus is involved in modulation of nociception. The Sm, ventrolateral orbital cortex (VLO) and the periaqueductal gray (PAG) constitute a pain modulatory pathway, activation of which leads to activation of the PAG–brainstem descending inhibitory system and depression of the nociceptive inputs in the spinal cord and trigeminal nucleus. Other studies have indicated that the Sm–VLO–PAG pathway plays an important role in the analgesia induced by electroacupuncture stimulation of the acupuncture point (acupoint) for exciting small diameter fiber (A-δ and C group) afferents. Opioid peptides, serotonin, dopamine, glutamate and their related receptors are involved in Sm- and/or VLO-mediated descending antinociception, and a GABAergic disinhibitory mechanism participates in mediating the antinociception induced by activation of μ-opioid receptors, serotonin 1_A receptors, and dopamine D₂-like receptors. This review describes these findings, which provide important new insights into the roles of the thalamus and cerebral cortex in descending pain modulation.