人参茎叶皂苷对热损伤大鼠糖皮质激素受体的影响

热应激可导致糖皮质激素受体 (GR)结合活性下降 [1 ] 。以往的研究 [2 ,3]证实 ,中医方剂“生脉饮”可降低热损伤时 GR结合活性的下降幅度。人参是“生脉饮”的君药 ,其主要有效成分是人参根皂苷。人参茎叶原为废弃物 ,但其所含的皂苷与人参根皂苷化学成分和药理活性基本一致 [4 ] 。人参茎叶皂苷 (GSS)是否也有调节 GR结合活性的作用 ?其作用机制是什么 ?本实验对这些问题进行了初步研究 ,现报告如下。1　材料和方法1.1　药物　 GSS(黑龙江东宁制药厂提供 ) ,纯度为91.6 7% ,配成 2 0、10、5 mg/ml 3个剂量的溶液待用。1.2　动物分组…     

人参茎叶皂苷对热损伤大鼠不同脏器糖皮质激素受体的影响

目的:观察人参茎叶皂苷(ginsenosides,GSS)对热损伤大鼠不同脏器糖皮质激素受体(glucocorticoidreceptor,GR)的影响,并探讨其作用机制。方法:雄性SD大鼠随机分为:(1)正常对照组,室温下饲养,蒸馏水灌胃;(2)GSS治疗组,室温下饲养,GSS灌胃;(3)热损伤模型组,蒸馏水灌胃,制作热损伤模型;(4)热损伤模型GSS治疗组,GSS灌胃,制作热损伤模型。采用放射配体结合法检测大鼠脑、胸腺、肺和肝细胞液GR结合活性;逆转录聚合酶链反应法测定脑、肝细胞液GRmRNA的水平;放射免疫法测定血浆促肾上腺皮质激素(adrenocorticotropin,ACTH)和皮质酮(corticosterone,CS)的浓度。结果:热损伤模型GSS治疗组大鼠脑、肺和肝细胞液GR结合活性以及脑和肝细胞液GRmRNA表达水平均明显高于单纯热损伤模型组(P<0.05或P<0.01);热损伤模型GSS治疗组大鼠血浆ACTH和CS浓度与单纯热损伤模型组比较则无明显差异。结论:GSS可缓解热损伤大鼠不同脏器GR结合活性的下降幅度,其作用机制可能与促进GRmRNA的表达有关。     

参附汤对失血性休克大鼠糖皮质激素及其受体的影响

深入探讨参附汤的药理作用机理。以急性失血性休克大鼠为实验对象，同步观察参附汤对血浆皮质酮及肝胞液，胸腺细胞糖皮质激素受体的影响。参附汤组大鼠肝胞液及胸腺细胞ＧＲ的结合位点都明显高于单纯失血组，参附汤组血浆皮质酮略高于失血组。参附汤可纠正失血性休克模型的ＧＲ的减少，以发挥其救治休克，回阳固脱的作用。     

参附汤对休克大鼠不同器官糖皮质激素受体的上调作用

目的：探讨参附汤临床益气回阳救逆功效的作用机制。方法：以失血性休克大鼠为模型，观察参附汤对失血性大鼠血浆皮质酮(GC)、促肾上腺皮质激素(ACTH)及脑、肝、胸腺等部位糖皮质激素受体(GCR)的影响。结果：参附汤对失血性休克大鼠脑、肝、胸腺等部位的糖皮质激素受体活性有明显的上调作用。结论：参附汤通过保护GCR，提高机体GC系统在失血性休克过程中的生物学效应，可能是其临床益气回阳救逆功效的重要作用机制之一；参附汤上调失血性休克大鼠糖皮质激素受体的作用未见器官特务性。     

人参茎叶皂甙对大鼠海马糖皮质激素受体及cAMP的影响

本实验探讨了以羟基磷灰石微量分析法测定大鼠海马内糖皮质激素受体（GR）的方法，实验结果表明，此方法是适用的，而且具有简便快速、节约标记物等特点，用此方法检测人参茎叶皂甙组大鼠海马GR的特异性结合量减少，下降率为48．2％，而结合力未见明显改变。同时发现人参茎叶皂甙组大鼠海马cAMP含是也下降，推测人参茎叶皂甙海马通过GR和cAMP的变化参入垂体一肾上腺轴的调节。     

人参茎叶皂甙对大鼠海马糖皮质激素受体及cAMP的影响

本实验探讨了以羟基磷灰石微量分析法测定大鼠海马内糖皮质激素受体(GR)的方法。实验结果表明:此方法是适用的,而且具有简便快速、节约标记物等特点,用此方法检测人参茎叶皂甙组大鼠海马GR的特异性结合量减少,下降率为48. 2％,而结合力未见明显改变。同时发现人参茎叶皂甙组大鼠海马cAMP含量也下降,推测人参茎叶皂甙海马通过GR和cAMP的变化参入垂体一肾上腺轴的调节。     

参芪注射液对大鼠失血性休克再灌注肠粘膜糖皮质激素受体的调节作用

目的 探讨参芪注射液对大鼠失血性休克-再灌注后肠粘膜组织糖皮质激素受体的影响.方法 雄性SD大鼠72只,随机分成:正常组、模型组、参芪低剂量组(参芪注射液10g/kg)和参芪高剂量组(参纸注射液20g/kg).对SD大鼠静脉使用肝素后缓慢放血,建立重度血失性休克及复苏的动物模型;参芪注射液于再灌注前静脉注入.造模完成后观察各组动物肠粘膜病理学变化,动态观察2,6、12 h肠粘膜、GR的结合活性和GRRNA的表达水平.结果 正常组肠粘膜无明显改变,模型组肠粘膜重度损伤,参芪高剂量组轻度损伤,低剂量组中度损伤;参芪高剂量组与低剂量组比较,肠粘膜损伤减轻程度更明显.模型组与正常组比较,2、6、12 h肠粘膜GR结合活性和GRmRNA表达明显降低(P<0.01);参芪注射液高低剂量组与模型组比较,2、6、12h肠粘膜GR结合活性和GRmRNA表达明显升高(P<0.01,P<0.05);参芪高剂量组与低剂量组比较,2、6、12h肠粘膜GR结合活性和GRmRNA表达升高更明显(P<0.05).结论 参芪注射液能有效地减轻大鼠失血性休克再灌注肠粘膜损伤,提高肠粘膜GR结合活性和GRmRNA的表达水平.     

人参皂甙对创伤失血性休克免疫功能的调节作用

目的 探讨人参皂甙（ＣＳ）对创伤失血性休克免疫功能的调节作用。方法 分体内实验和体外实验两个部分。体现人实验：给大鼠ＣＳ预处理３天后进行创伤失血性休克模型的５复制，１天后处死动物，分别测定淋巴细胞和巨噬细胞的功能；体外实验；创伤失血性休克后１天处死动物，分离、纯化淋巴细胞和腹腔巨噬细胞，观察ＣＳ对免疫功能的影响。结果 一正常对照组大鼠相比，创伤人血性休克１天大鼠脾淋巴细胞增殖、ＩＬ－２活性、ＩＬ－     

人参皂苷通过上调糖皮质激素受体表达对AIH小鼠肝脏的保护作用

目的 研究人参皂苷通过调节糖皮质激素受体与骨髓源性免疫抑制细胞（myeloid-derived suppressor cell, MDSC）增殖改善自身免疫性肝炎(autoimmune hepatitis, AIH)的机制。方法 小鼠分组为空白组、模型组、人参皂苷（AIH+GSS）组与地塞米松（AIH+DEX）组。使用S-100与佐剂构建AIH小鼠模型,以地塞米松作为阳性对照。通过流式细胞术检查外周血MDSC、调节性T细胞（regulatory T cell, Treg）、辅助性T细胞17 (T helper 17 cell, Th17)细胞比例,检测血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase, AST)活性,通过HE、Masson染色检查肝脏病理,分离外泌体并检测miRNA-223的表达情况,检查糖皮质激素受体（glucocorticoid receptor, GR）、精氨酸酶1(arginase type 1, Arg-1)、一氧化氮合酶（nitric oxide synthases,...     

生脉注射液对失血性休克大鼠的作用

目的观察生脉注射液对失血性休克大鼠血压、心电图、心率等的作用。方法大鼠用20%乌拉坦(5ml/kg)腹腔注射麻醉后,分离双侧颈动脉,一侧颈动脉迅速放血使血压降至40.8mmHg左右,并维持血压稳定10min,完成失血性休克模型的建立。另一侧做颈动脉插管,连接压力换能器,用来观察血压的变化,同时记录心电图。之后,静脉注射给药。结果生脉注射液能够明显提升失血性休克大鼠的收缩压、舒张压及平均动脉血压,改善休克状态,提高存活率。结论生脉注射液具有抗失血性休克作用。     

CB1 cannabinoid receptor participates in the vascular hyporeactivity resulting from hemorrhagic shock in rats

Background Vascular hyporeactivity, which occurs in the terminal stage of hemorrhagic shock, is believed to be critical for treating hemorrhagic shock. The present study was designed to examine whether the CB1 cannabinoid receptor （CB1 R） was involved in the development of vascular hyporeactivity in rats suffering from hemorrhagic shock. Methods Sixteen animals were randomly divided into two groups （n=8 in each group）： sham-operated （Sham） and hemorrhagic shock （HS） groups. Hemorrhagic shock was induced by bleeding. The mean arterial pressure （MAP） was reduced to and stabilized at （25±5） mmHg for 2 hours. The vascular reactivity was determined by the response of MAP to norepinephrine （NE）. In later experiments another twelve animals were used in which the changes of CB1R mRNA and protein in aorta and superior mesenteric artery （SMA） were analyzed by RT-PCR and Western blotting. In addition, we investigated the effects of a CB1R antagonist on the vascular hyporeactivity and survival rates in rats with hemorrhagic shock. Survival rates were analyzed by the Fisher＇s exact probability test. The MAP response was analyzed by one-way analysis of variance （ANOVA）. Results Vascular hyporeactivity developed in all animals suffering from hemorrhagic shock. The expression of CBIR mRNA and protein in aorta and 2-3 branches of the SMA were significantly increased in the HS group after the development of vascular hyporeactivity when compared to those in Sham group. When SR141716A or AM251 was administered, the MAP response to NE was （41.75±4.08） mmHg or （44.78±1.80） mmHg respectively, which was higher than that in saline groups with （4.31±0.36） mmHg （P 〈0.01）. We also showed an increased 4-hour survival rate in the SR141716A or AM251-treated group with 20% or 30%, but with a statistically significant difference present between the AM251-treated and saline groups （P 〈0.05）. Conclusions CBIR is involved in vascular hyporeactivity resulting from hemorrhagic shock in rats, and CB1R antagonist may be useful in treating patients with traumatic, hemorrhagic shock who need field-rescue or initial treatment.     

生脉散组分配伍对热损伤大鼠糖皮质激素受体的影响

目的：研究生脉散组分配伍对热损伤大鼠糖皮质激素受体（glucocorticoid receptor,GR）的影响。 方法：雄性SD大鼠32只随机分为正常对照组、模型组、人参总皂苷组和生脉散组分配伍组（简称组分配伍组）,每组8只,连续灌胃1周进行预处理。除正常对照组外,其余各组大鼠于末次给药30min后复制大昂热损伤模型。随后立即断头处死动物,收集血清和肝、肺、肾脏组织。酶联免疫吸附测定法（enzyme-linked immkinosorbent assay,ELISA）检测血清皮质酮（corticosterone,CS）的浓度,放射免疫检测法（radioimmunoassay,RIA）检测血清促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）的浓度;放射性配体受体结合法（radioligand receptor binding assay,RRA）检测肝、肺、肾细胞液GR结合容量。 结果：模型组肝、肺、肾胞液GR明显低于正常对照组（P〈0.01）。组分配伍组肝和肺胞液GR结合容量明显高于模型组（P〈0．01）,肾胞液GR结合容量与模型组比较,差异无统计学意义。组分配伍组肝胞液GR明显高于人参总皂苷组（P〈0．01）,肺和肾胞液GR结合容量与人参总皂苷组比较有上升的趋势．但差异无统计学意义。正常大鼠CS及ACTH水平与模型组、组分配伍组和人参总皂苷组比较,差异有统计学意义（P〈0．01）,模型组CS及ACTH水平与各给药组比较,差异无统计学意义。 结论：生脉散组分配伍可增强人参总皂苷上调热损伤大鼠GR水平的作用。     

Regulation of vascular function by opioid receptor in the arterial wall during hemorrhagic shock in rats

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糖皮质激素受体在创伤失血性休克大鼠肝损伤中的作用

目的 从组织受体水平探讨糖皮质激素受体(GR)在创伤失血性休克后肝组织中的变化及其对肝损伤的作用机制.方法 采用双侧股骨骨折伴失血性休克模型,并对GR进行阻断后再致伤,动态观察伤后8h大鼠肝组织GR、肝脏病理、肝功能生化指标、伤后8h大鼠死亡率等变化.肝组织GR采用免疫印迹法测定其蛋白含量,并进行计算机图像分析.结果 肝组织GR的蛋白含量在创伤失血性休克后1h即开始下降,2h明显低于正常对照组(P＜0.01),6h降至最低,8h仍显著低于正常;光镜下伤后4h-8h肝窦内少许淤血,有散在炎性细胞浸润;血清丙氨酸氨基转移酶(ALT)、总胆红素(TB)伤后4h开始增高,白蛋白下降;大鼠死亡率10%.GR阻断后再致双侧股骨骨折并失血性休克,光镜下伤后2h肝窦内即可见较多炎性细胞浸润,血清ALT、TB在伤后2h即有明显升高(P＜0.01),白蛋白明显下降(P＜0.01);大鼠死亡率明显升高(50%).结论 GR不足可导致严重创伤并失血性休克后肝损伤的发生;且减少越多,肝损害越重,死亡率越高.提示GR在严重创伤休克后肝组织细胞损伤与抗损伤机制方面可能起着重要作用.     

非控制性出血性休克低压复苏治疗效果的研究

目的　应用大鼠脾损伤非控制性出血性休克模型探讨低压及低压扩容复苏治疗非控制性出血性休克的可行性。方法　雄性Wistar大鼠 5 0只 ,在大鼠脾损伤模型复制成功后随机等分为 5组 ,组 1 :假手术组 ;组 2 :休克未处理组 ;组 3:常压复苏组 (急救期控制MAP在 80mmHg以上 ) ;组 4 :低压复苏组 (急救期控制MAP在 6 0mmHg±5mmHg) ;组 5 :低压扩容复苏组 (急救期输入硝普钠 5 μg·kg- 1 ·min- 1 ,同时输液控制MAP在 6 0mmHg± 5mmHg)。结果　 1～ 5组平均存活时间 (min)分别为 1 80、73.5 0± 8.0 4、1 1 4 .30± 31 .33、1 4 6 .70± 2 8.0 7和 1 71 .6 0± 1 5 .74 ,除组1、组 5外 (P =0 .0 6 71 ) ,其余各组间比较均有统计学意义 (P <0 .0 5 ) ;2～ 5组的急救期出血量 (ml·kg- 1 )分别为 :3.79± 1 .39、1 7.4 1± 8.88、8.6 7± 4 .5 9、1 0 .33± 4 .31 ,其中组 3出血量明显高于其他各组 (P <0 .0 1 ) ;组 4、组 5与组 2比较出血量明显增多 (P <0 .0 5 )。结论　在非控制性出血性休克治疗中 ,低压及低压复合适量硝普钠扩容复苏方法可改善组织代谢 ,提高生存时间 ,是更为理想的复苏方法     

The glucocorticoid resistance in burn and shock

The changes of glucocorticoid receptor (GR) and the reactivity of target cells toglucocorticoids (GC) were studied experimentally.The results showed that GC resistance,which wascaused mainly by the decrease of GR,developed in burned and shocked rats and dogs.Thesechanges may exacerbate the shock state,and even lead to the development of multiple organfailuue.The protection of GC against intestinal ischemic shock of dogs was demonstrated after theconcentration of dexamethasone (Dex) in plasma was elevated to 10~(-6) mol/L by iv injection of 5mgDex/kg body weight.     

Effects of glycine and methylprednisolone on hemorrhagic shock in rats

Background Methylprednisolone (MP), a synthetic glucocorticosteroid, has been broadly studied in experiments on endotoxin-induced shock and septic shock. This study was designed to ascertain whether glycine and MP can protect against organ injury and death caused by hemorrhagic shock, and to elucidate the underlying mechanisms of these protective effects in rats.Method To establish a shock model, Wistar rats were bled to maintain mean arterial pressure at 30-50 mmHg for 1 hour and subsequently resuscitated with the shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to four groups: sham group (operation performed without inducing shock), shock group, shock+glycine group (glycine injected at the beginning of resuscitation) and shock+MP group (MP injected at the beginning of resuscitation).Results ① Seventy-two hours after resuscitation, the survival rate of rats from the shock group had decreased to 20%, while the survival rates of rats from the shock+glycine and shock+MP groups were 77.8% and 80%, respectively. The difference was significant (P&lt;0.05). ② Eighteen hours after resuscitation, pathological alterations in the organs of the rats were apparent. In rats from the shock group, edema, interstitial leukocyte infiltration, and cellular degeneration occurred in the liver, lungs, kidneys, and heart. Glycine and MP reduced these pathological changes significantly. ③ Eighteen hours after resuscitation, the levels of creatine phosphokinase, transaminases, and creatine were elevated significantly in rats from the shock group, indicating injury to the heart, liver, and kidneys, while these levels were elevated only slightly in the shock+glycine and shock+MP groups. The differences were significant (P&lt;0.01). ④ There were significant increases in intracellular calcium and production of tumor necrosis factor (TNF-α) by isolated Kupffer cells stimulated by endotoxin after hemorrhagic shock. These changes were completely prevented by glycine and MP (P&lt;0.01). Conclusion Glycine and MP reduce organ injury and mortality caused by hemorrhagic shock by preventing increase of intracellular calcium levels in Kupffer cell, suppressing Kupffer cell activation, decreasing the production of TNF-α by Kupffer cells, and blocking systemic inflammatory responses.