CARDIOVASCULAR RESPONSES TO SIMULATED MICROGRAVITY IN SPRAGUE-DAWLEY RATS

Microgravity is known to induce orthostatic intolerance and baroreflex impairment in astronauts. Cardiovascular responses observed in 30° head-down tilt rat models, whether 24 hr whole body suspension (WBS) or 7 day tail-suspension (TS), mimic observations made during exposure to microgravity. We evaluated the cardiovascular effects of simulated microgravity and the subsequent post-suspension in rats using the above models. Mean arterial pressure (MAP) of both WBS and TS rats did not change during suspension. In both models, MAP decreased post-suspension and this response lasted for 6 hrs. Salt-loaded animals did not show a post-suspension reduction in MAP. Plasma ionized calcium was decreased at 2 hr of WBS, with no change in sodium, potassium, magnesium, glucose, or hematocrit. Body weight changes were similar for all animals whether under suspension or control conditions. Both rat models demonstrate post-suspension hypotension and these results support the notion that salt-loading may have some beneficial effects in ameliorating this hypotension.     

Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats

Late phase airflow obstruction and reduction in forced vital capacity are characteristic features of human asthma. Airway microvascular leakage and lung edema are also present in the inflammatory phase of asthma, but the impact of this vascular response on lung functions has not been precisely defined. This study was designed to evaluate the role of increased lung microvascular leakage and edema on the late phase changes in forced vital capacity (FVC) and peak expiratory flow (PEF) in allergen-challenged Brown Norway rats using pharmacological inhibitors of the allergic inflammatory response. Rats were sensitized and challenged with ovalbumin aerosol and forced expiratory lung functions (FVC, PEF) and wet and dry lung weights were measured 48 h after antigen challenge. Ovalbumin challenge reduced FVC (63% reduction) and PEF (33% reduction) and increased wet (65% increase) and dry (51% increase) lung weights. The antigen-induced reduction in FVC and PEF was completely inhibited by oral treatment with betamethasone and partially attenuated by inhibitors of arachidonic acid metabolism including indomethacin (cyclooxygenase inhibitor), 7-TM and MK-7246 (CRTH2 antagonists) and montelukast (CysLT₁ receptor antagonist). Antagonists of histamine H₁ receptors (mepyramine) and 5-HT receptors (methysergide) had no significant effects indicating that these pre-formed mast cell mediators were not involved. There was a highly significant (P < 0.005) correlation for the inhibition of FVC reduction and increase in wet and dry lung weights by these pharmacological agents. These results strongly support the hypothesis that lung microvascular leakage and the associated lung edema contribute to the reduction in forced expiratory lung functions in antigen-challenged Brown Norway rats and identify an important role for the cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in these responses.     

栝楼瞿麦丸对糖尿病肾病大鼠肾脏保护作用的实验研究

[目的]以实验性糖尿病肾病(DN)大鼠为研究对象,观察并探讨<金匮要略>栝楼瞿麦丸对肾脏病变的治疗作用.[方法]将80只雄性SD大鼠随机分为5组,即空白对照组,模型组,栝楼瞿麦丸低剂量组,中剂量组,高剂量组.采用左肾切除、尾静脉注射链脲佐菌素(STZ)的方法造模后,依不同剂量分别给药共6周.于第6周末检测尿量,尿蛋白,尿素氮,血肌酐,计算肌酐清除率.[结果]栝楼瞿麦丸可减少尿蛋白排泄,降低血肌酐、尿素氮水平.[结论]栝楼瞿麦丸对糖尿病肾病大鼠肾功能有一定的保护作用.     

壳聚糖对大鼠的致畸胎试验

背景与目的:通过在胚胎器官形成期连续给药,观察壳聚糖对大鼠的胚胎毒性和致畸毒性.材料与方法:将90只妊娠SD大鼠按时间先后随机分为5组,即阴性对照组、壳聚糖50、250、1000 mg/k剂量组和阳性对照组,每组18只.在大鼠胚胎器官形成期(妊娠的第6～15 d),壳聚糖各剂量组和阴性对照组连续给受试物10 d,每日经口灌胃分别给予壳聚糖和生理盐水,阳性对照组在孕期第11～13 d每天腹腔注射环磷酰胺(cyclophosphamide,CP)7 mg/kg,在妊娠的第20 d处死大鼠进行胎鼠检查.结果:壳聚糖对孕鼠的健康状况、行为、增重和生殖机能无明显影响;对胎鼠的生长发育无明显影响;对胎鼠的外观、骨骼和内脏无致畸作用.结论:在≤1000 mg/kg剂量下,壳聚糖对大鼠无胚胎毒性和致畸毒性.     

选择性COX-2抑制剂NS398干预后对HIBD新生大鼠海马CA1区存活锥体细胞计数的变化

目的研究新生大鼠缺氧缺血性脑损伤(HIBD)时应用选择性COX-2抑制剂NS398干预后海马CA1区存活锥体细胞计数的变化。方法于制备新生大鼠左脑的HIBD模型前30min,应用腹部注射NS39820mg/kg,同时建立未注射HIBD组及对照组,于HIBD后7d,测试左侧海马CA1区存活锥体细胞数。结果统计学比较,HIBD组CA1区存活锥体细胞计数显著低于对照组;NS398干预组存活锥体细胞数显著高于HIBD组。结论应用选择性COX-2抑制剂NS398可以减少新生鼠HIBD时锥体细胞缺失。     

NF—κB、TNF—α在淹溺大鼠脑组织中的表达及其与脑损伤的相关性

目的:探讨淡水淹溺后大鼠脑组织中细胞因子NF-κB、TNF-α的表达及其与淹溺应激引起脑损伤之间的关系。方法:Wistar大鼠70只,其中正常对照(Ⅰ组)、溺水致死(Ⅱ组)、溺水后存活(Ⅲ组)3h、6h、12h、24h、40h各10只,剥取脑组织固定、切片,HE染色后光镜下观察形态学改变;SABC免疫组化法检测各组大鼠脑组织中NF-κB、TNF-α的表达。结果:Ⅰ组脑组织结构清晰,无水肿、出血、坏死病灶;Ⅱ组脑实质疏松,小血管周隙增宽,部分神经细胞体积增大变性;Ⅲ组随溺水后存活时间的推移,脑损伤程度逐渐加重,其中24h脑水肿最重,40h个别脑实质小灶性液化性坏死。Ⅱ组脑指数明显高于Ⅰ组(P<0.05),并高于Ⅲ组,与3h、6h、12h差异有统计学意义(P<0.05)。与Ⅰ组相比,Ⅲ组6h时NF-κB表达显著增加(P<0.05);12h时TNF-α表达显著增加(P<0.05)。结论:淡水淹溺后存活大鼠发生脑损伤时NF-κB和TNF-α高表达,提示NF-κB、TNF-α与淹溺应激所致脑损伤有关。     

川芎嗪与阿魏酸配伍对大鼠心肌缺血再灌注损伤心肌的保护作用

目的:观察川芎嗪与阿魏酸配伍对大鼠心肌缺血再灌注损伤的保护作用。方法:将健康雄性SD大鼠64只,随机分为4组,每组16只。分别为正常组、假手术组、模型组及川芎嗪与阿魏酸配伍组。后2组制备大鼠急性心肌缺血再灌注损伤模型。造模6h后检测血清肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)、心肌超氧化物歧化酶(SOD)、丙二醛(MDA);24h后取心脏,RT-PCR法检测细胞间黏附分子(ICAM-1)、P-选择素、E-选择素mRNA表达。结果:川芎嗪与阿魏酸配伍可明显降低心肌缺血再灌注损伤大鼠血清CK(P<0.01);但对血清LDH以及心肌SOD和MDA作用不明显(P>0.05);还可显著降低E-选择素、P-选择素mRNA表达(P<0.01)。结论:川芎嗪与阿魏酸配伍对大鼠心肌缺血再灌注损伤心肌有明显的保护作用。     

复合离子盐对两肾一夹高血压大鼠心肌肥厚的影响

目的:研究复合离子盐对两肾一夹高血压大鼠心肌肥厚的影响。方法:将80只Wistar大鼠喂含8%普通盐饲料1周后,70只行二肾一夹经典造模,10只行假手术。将造模成功的大鼠随机分为4组(每组10只):离子盐组、缬沙坦组、环孢菌素A组、普通加碘盐组。12周后,测量比较各组收缩压(SBP)、左室质量与胫骨长度比值(Lvw/TL)、胶原总面积/图像总面积(CVF)、心肌Ⅰ、Ⅲ型胶原比值(RatioⅠ/Ⅲ)、壁内小动脉管腔周围胶原面积/壁内小动脉管腔面积(PVCA)、血管紧张素Ⅱ(Ang-Ⅱ)、醛固酮(ALD)、内皮素(ET)、一氧化氮(NO)和心钠素(ANP)水平。结果:离子盐组Ang-Ⅱ、ANP、Lvw/TL、ALD、ET、CVF、SBP水平低于普通盐组(P<0.05或P<0.01),NO、RatioⅠ/Ⅲ水平高于普通盐组(P<0.01);缬沙坦组Ang-Ⅱ、NO、RatioⅠ/Ⅲ水平高于普通盐组(P<0.01),ET、ANP、CVF、PVCA、SBP、Lvw/TL水平低于普通盐组(P<0.01);环孢菌素A组ANP、Lvw/TL水平低于普通盐组(P<0.01),RatioⅠ/Ⅲ水平高于普通盐组(P<0.01)。离子盐组Ang-Ⅱ、ALD水平低于缬沙坦组(P<0.01),CVF、SBP水平高于缬沙坦组(P<0.01);环孢菌素A组ET、ANP、RatioⅠ/Ⅲ、CVF、SBP、Lvw/TL水平高于缬沙坦组(P<0.05);NO水平低于缬沙坦组(P<0.01)。离子盐组Ang-Ⅱ、ALD、ANP、RatioⅠ/Ⅲ和SBP水平低于环孢菌素A组(P<0.05),NO、ET、CVF、PVCA、Lvw/TL水平2组差异无统计学意义(P>0.05)。结论:复合离子盐能够改善高血压性心肌肥厚,其作用接近于降压剂量的缬沙坦。     

孟加拉玫瑰红诱导的激光所致大鼠缺血性视神经病变模型制作

目的:视神经损伤是以视网膜神经节细胞的轴突损害为主要特征,所以研究缺血性视神经病变模型以抑制视神经节细胞损伤对于人类治疗致盲性眼病具有重大意义.方法:大鼠60只,双眼分别为孟加拉玫瑰红注射实验组、孟加拉玫瑰红注射 激光实验组、激光实验组和空白对照组,用25g/L乌拉坦10mL/kg麻醉,ip.结果:用孟加拉玫瑰红尾部注射和单纯激光的方法均不能产生视网膜缺血.用孟加拉玫瑰红诱导后,用激光的方法可以成功制作缺血性视神经病变模型,并在闪光VEP、视网膜血液供应、光镜、电镜、定量观察等方面都有相应的改变.结论:用孟加拉玫瑰红诱导激光可成功制作缺血性视神经病变模型