人参皂苷Rg1对DSS诱导溃疡性结肠炎小鼠凝血功能的调节作用

[目的]探讨中药三七有效成分人参皂苷Rg1治疗溃疡性结肠炎(UC)的可能机制.[方法]采用5％葡聚糖硫酸钠(DSS)建立UC小鼠模型,将小鼠随机分为人参皂苷Rg1高剂量组、人参皂苷Rg1低剂量组、美沙拉嗪肠溶片(5-ASA)组、模型1组、模型2组和正常组(每组10只).模型1组于造模7d处死,其余各组于造模第7天开始灌胃给药,连续给药7d处死.小鼠眼球采血检测凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT);放免法检测血浆中血栓素B2(TXB2)、6-酮前列腺素F1α(6-keto-PGF1α)含量.[结果]与正常组相比,模型1组及模型2组PT、APTT、TT明显缩短(P＜0.01),血浆TXB2明显升高(P＜0.01),6-keto-PGF1 α降低(P＜0.01),TXB2/6-keto-PGF1α比值升高(P＜0.01);人参皂苷Rg1高剂量组、人参皂苷Rg1低剂量组、5-ASA组经用药干预后,PT、APTT、TT均有不同程度的延长,血浆TXB2水平降低、6-keto-PGF1α表达增加,与模型1组和模型2组比较差异有统计学意义(P＜0.01).[结论]人参皂苷Rg1可延长出凝血时间,下调血浆TXB2水平,上调6-keto-PGF1α含量,缓解UC小鼠的血液高凝状态,改善机体微循环,从而抑制或降低炎症反应的扩大,以达到缓解UC的症状作用.     

人参二醇组皂苷对感染性休克大鼠血液流变性及微循环的影响

目的 观察人参二醇组皂苷(PDS)对感染性休克大鼠血液流变性及微循环的影响,探讨其抗感染性休克的作用机制.方法 大鼠舌下静脉注射PDS进行预治疗,10 min后注射细菌内毒素(LPS 5 mg/kg)复制感染性休克模型.实验动物随机分为对照组(S组);内毒素休克模型组(L组);地塞米松预治疗组(LD组);PDS预治疗(22.5 mg/kg,LP_小)(45 mg/kg,LP_中)(90 mg/kg,LP_大)组.各组于休克后观察肠系膜微循环的变化,2 h和4 h腹主动脉取血,测量全血黏度.结果 模型组在休克2 h、4 h全血黏度明显高于PDS各剂量组(P＜0.01).肠系膜微循环的变化:PDS各剂量组在休克2～4 h微动脉管径、微动脉血流速度及微动脉管袢数均高于模型组(P＜0.05).结论 PDS通过降低内毒素休克大鼠全血黏度,改善微循环状态,起到抗休克的作用.     

人参二醇组皂苷抗动脉粥样硬化的作用及机制

目的 探讨人参二醇组皂苷(PDS)的抗动脉粥样硬化作用及机制.方法 Wistar大鼠45只,随机分为对照组、模型组、PDS组,每组15只.对照组大鼠喂饲普通饲料,模型组及PDS组大鼠采用高脂饮食加维生素D3(总量7×10~5 U/kg,分别于第1周和第6周腹腔注射)建立大鼠动脉粥样硬化模型.PDS组大鼠高脂喂养同时每日1次PDS(100 mg·kg~(-1)·d~(-1))灌胃,每周称重1次并根据体重变化调整给药量;对照组及模型组大鼠以相应生理盐水灌胃.11 w后颈动脉采血检测血脂水平,光镜下观察主动脉弓形态学变化,免疫组化染色法检测胸主动脉细胞间黏附分子-1(ICAM-1)的表达.结果 与模型组比较,PDS给药组TC、LDL-C和AI明显降低(P<0.01,P<0.05),血清甘油三酯、高密度脂蛋白水平无明显差异.光镜下模型组血管壁多处可见典型粥样硬化斑块,药物组血管壁结构变化轻微,局部仅见内皮脱落;对照组血管壁光滑完整,未发生病理变化.免疫组织化学染色结果显示,模型组阳性细胞率与对照组比较明显升高(P<0.01);与模型组比较,PDS组阳性细胞率明显降低(P<0.01);而PDS组阳性细胞率与对照组无明显差异.结论 PDS具有预防动脉粥样硬化形成的作用,通过下调主动脉ICAM-1的表达量,抑制AS的形成.     

人参二醇组皂苷改善内毒素诱导急性肾损伤小鼠肾功能的机制

目的探讨人参二醇组皂苷(PDS)对内毒素(LPS)诱导的急性肾损伤(AKI)小鼠肾功能的保护作用及机制。方法选择C57BL/6小鼠随机分成3组(n=8),分别为对照组(control,腹腔注射0.9%氯化钠),LPS组(腹腔注射LPS 10 mg/kg),PDS+LPS组(先腹腔注射PDS 25 mg/kg,1 h后注射LPS 10 mg/kg)。注射LPS 12 h后麻醉下处死小鼠,取肾脏组织冻存或固定,备蛋白表达与形态学观察用,并收集血液用于生化检测。利用免疫组化方法观察形态学变化。利用免疫印迹方法测定肾脏相关蛋白含量及表达情况。结果 LPS组小鼠肾组织凋亡严重,肝肾功能明显异常,而PDS+LPS组肾脏组织凋亡及肝肾功能损伤较LPS组轻(P<0.05)。LPS组一氧化氮合成酶(iNOS)蛋白表达水平和NO含量与对照组比较明显增加(P<0.05)。而PDS+LPS组iNOS蛋白表达水平和NO含量均显著低于LPS组(P<0.05)。LPS组肾脏丙二醛(MDA)含量与对照组比较明显增高(P<0.05),超氧化物歧化酶(SOD)含量和Mn-SOD的蛋白表达水平都明显低于对照组(P<0.01,P<0.05),而PDS+LPS组MDA含量较LPS组低(P<0.05),SOD含量和Mn-SOD的蛋白表达水平较LPS组高(P<0.05)。结论 PDS有逆转LPS诱导的AKI小鼠肾功能的作用,其保护作用机制为抑制肾脏iNOS表达,减少NO产生与释放,抑制MDA的产生和上调SOD的表达而起到抗氧化应激的作用。     

人参二醇组皂苷对失血性休克犬心肌收缩功能和血氧饱和度的影响

目的观察人参二醇组皂苷(Panaxdiols Saponin,PDS)对失血性休克犬心肌收缩功能、血氧分压(PaO2)、血氧饱和度(SaO2)及红细胞压积(HCT)的影响。方法制备犬失血性休克病理模型,动脉放血至平均动脉压(MAP)在5.33kPa以下,然后静脉滴注PDS12.5,25mg/kg,地塞米松磷酸钠注射液(DXMT)1mg/kg。测定犬心肌收缩功能、动脉血气和HCT的变化。结果 PDS使失血性休克犬MAP、左室收缩压(LVSP)及左室内压最大变化速率(±dp/dtmax)显著升高;血气PaO2和SaO2明显上升;HCT下降。结论 PDS可明显改善失血性休克犬血流动力学状态,提高血氧含量,减轻组织缺血缺氧及微循环障碍,对失血性休克犬具有保护作用。     

人参二醇组皂苷对心肌梗死后心室重构大鼠心脏形态学及血流动力学的影响

目的研究人参二醇组皂苷(Panaxadiol Saponins,PDS)对心肌梗死后心室重构大鼠心脏形态学及血流动力学的影响。方法通过结扎大鼠左冠状动脉前降支造成心肌梗死后心室重构模型。将W istar大鼠随机分成假手术组、模型组、PDS组及卡托普利组。假手术组及模型组腹腔注射生理盐水2ml.kg-1.d-1,PDS组腹腔注射人参二醇组皂苷50mg.kg-1.d-1,卡托普利组灌胃卡托普利100mg.kg-1.d-1。给药4w后观察各组大鼠心脏形态学,血流动力学及组织病理学等参数。结果 PDS能明显降低心室重构大鼠心室脏器指数,升高平均动脉压(MAP)、左心室内压最大上升和下降速率(±dp/dtmax),降低左心室舒张末压(LVEDP)。此外,PDS还可明显减轻心室重构大鼠心肌组织病理损伤。结论 PDS对大鼠心肌梗死后心室重构具有保护作用。     

TRPV6在人参二醇组皂苷(PDS)减轻LPS休克脑损伤中表达的变化及意义

RPV6的蛋白表达水平明显降低,Bcl-2/Bax蛋白表达的比值降低;而与LPS组相比,LPS+Dex组和LPS+PDS各组大鼠生存率增加,脑皮质中TRPV6的蛋白表达水平明显增高,Bcl-2/Bax比值也增高. 结论 PDS减轻LPS诱导的脑损伤,可能与上调脑皮质中TRPV6蛋白有关.     

人参二醇皂苷对感染性休克大鼠血清心肌酶和心肌超微结构的影响

目的观察人参二醇皂苷(PDS)对感染性休克大鼠心肌酶和心肌细胞超微结构的影响。方法大鼠舌下静脉注射PDS进行预治疗,10min后注射细菌内毒素(LPS,5mg/kg)复制感染性休克模型。实验动物随机分为对照组;LPS组;地塞米松(LPS+Dex)组;人参二醇皂苷(LPS+PDS)组。颈动脉插管记录平均动脉压(MAP);分别于休克后2h和4h腹主动脉取血,测定天门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)含量及电镜观察心肌细胞超微结构的改变。结果注射LPS后,LPS组的MAP迅速下降,在低水平维持,LPS+Dex组和LPS+PDS组的MAP未见明显下降,优于模型组(P0.01);注射LPS4h后LPS组的AST、CK、LDH均明显升高,LPS+Dex组和LPS+PDS组心肌酶含量显著低于LPS组(P0.01)。结论 PDS能够明显改善LPS休克大鼠的低血压状态,降低心肌酶活性,减轻心肌细胞超微结构的损伤程度。     

20(s)-原人参二醇、人参皂苷Rh_2及人参皂苷Rg_3抗肿瘤作用的对比

目的对比20(s)-原人参二醇(Ppd)与人参皂苷Rh2(Rh2)及人参皂苷Rg3(Rg3)的抗肿瘤作用。方法建立小鼠肝癌H22、Lewis肺癌及黑色素瘤B16三种移植瘤动物模型,将小鼠随机分成11组,对照组给予0.5%羧甲基纤维素钠,阳性药组给予环磷酰胺(CTX)30 mg/kg,Ppd、Rh2及Rg3三个剂量组均给予相应受试药25、50、100 mg/kg。阳性药组隔日腹腔注射给药1次,其余各组均每日灌胃给药1次,给药容积为20 ml/kg,连续10 d。每天记录小鼠体重,末次药后称取小鼠体重及肿瘤重量并计算肿瘤抑瘤率。结果 Ppd、Rh2及Rg3在25、50、100 mg/kg剂量下,对肝癌H22、Lewis肺癌及黑色素瘤B16均有一定的抑瘤作用,仅Ppd在50、100 mg/kg剂量下对肝癌H22、Lewis肺癌及黑色素瘤B16抑制效果明显,其抑瘤率超过40%,Rh2与Rg3的抑瘤率无明显差别。结论 Ppd、Rh2及Rg3对小鼠三种移植瘤均具有抗肿瘤活性,以Ppd的抗肿瘤作用最明显,Rh2与Rg3之间无明显差别。     

西洋参叶20s-原人参二醇组皂苷对大鼠实验性心室重构的影响

目的 研究西洋参叶20s-原人参二醇组皂苷(PQDS)对大鼠急性心肌梗死晚期缺血再灌注后心室重构的影响及机制.方法 大鼠结扎左冠状动脉前降支2 h后,松扎再灌注28 d制备急性心肌梗死晚期缺血再灌注后心室重构模型,同时应用PQDS治疗,给药28 d后测定心室重构大鼠心脏形态学参数,血浆血管紧张素Ⅱ(ATⅡ)及内皮素(ET)水平.结果 与心室重构模型组比较,PQDS 50、100 mg·kg~(-1)·d~(-1)均能显著降低非梗死区室间隔厚度及左室腔面积/左室总面积比值(P<0.05及P<0.01),减少梗死区胶原沉积(P<0.05),降低非梗死区Ⅰ型及Ⅲ型胶原蛋白比值(P<0.05),并显著降低血浆ATⅡ及ET水平(P<0.05及P<0.01).两组间各项指标无显著差异. 结论 PQDS能够抑制大鼠实验性心肌梗死晚期缺血再灌注后的心室重构,其机制可能与降低血浆ATⅡ及ET水平,改善胶原重构相关.     

Effects of insulin infusion on endothelium-derived vasoactive substances

Summary An association between insulin resistance and hypertension has been reported in several studies. In apparent contradiction, insulin infusion in healthy volunteers is associated with vasodilatation. Furthermore, there is evidence that some insulin effects may differ between the sexes. We performed three-step hyperinsulinaemic-euglycaemic clamp studies in six men and six women to test the hypotheses that: 1) insulin might affect the release of vasoactive substances by the endothelium, and 2): this putative effect on vasoactive substances might differ between men and women. Six other women and six men served as control subjects, receiving 154 mmol/l NaCl (saline) infusion. Plasma levels of insulin, immunoreactive endothelin, l-arginine (precursor of nitric oxide), l-citrulline (by-product of nitric oxide synthesis) and cyclic GMP (second messenger of nitric oxide) were measured during infusion of insulin or 154 mmol/l NaCl (saline), respectively. We also assessed urinary excretion of 6-keto PGF-1α (a degradation product of prostacyclin reflecting prostacyclin production). Blood pressure was monitored in all subjects throughout the experiment. In women plasma levels of immunoreactive endothelin decreased from (mean ± SD) 2.58 ± 0.96 to 1.7 ± 0.72 pmol/l during insulin infusion (p < 0.01), while remaining constant in female control subjects (p < 0.02). No changes in levels of endothelin were observed in men during infusion of insulin or saline. In women levels of cGMP rose and levels of l-arginine decreased significantly during insulin infusion, consistent with an increase in nitric oxide production. Excretion of 6-keto PGF-1α also increased significantly in women during insulin infusion. No such effects were observed in men, or in women during infusion of saline. Blood pressure remained constant in all subjects during hyperinsulinaemia. We conclude that sex differences exist in the effects of insulin on the endothelium. Short-term hyperinsulinaemia in women is associated with a decline in levels of immunoreactive endothelin, and possibly with a rise in production of nitric oxide and prostacyclin. In contrast, levels of vasoactive substances remained constant in men during hyperinsulinaemia. Our findings may partly explain insulin's vasodilatory effects in healthy individuals. It remains to be investigated whether these effects are lost in insulin-resistant states. Our observation that there is a sex difference in insulin effects on the endothelium may help explain why the link between hyperinsulinaemia and cardiovascular disease appears to be clearer in men than in women. [Diabetologia (1996) 39: 1284–1292] Received: 30 April 1996 and in revised form: 18 July 1996     

Catecholamines and other vasoactive substances in blood in cardiogenic shock]

The blood levels of catecholamines, serotonin, histamine and acetylcholine were studied in 17 patients with severe and moderate coronary shock. The blood level of the above vasoactive substances varied widely, and no clear regularity was noted in the changes of the content of the catecholamines, histamine, serotonin and acetylcholine. A relatively higher (on the average) level of noradrenaline was noted in severe shock, in contrast to the moderate cases, as well as a relatively low level of noradrenaline and acetylcholine in the blood of patients with a full atrioventricular block and bradycardia. In studying the vasoactive substances dynamically similar, phase-like fluctuations of the blood level of histamine and serotonin were noted in some patients. In a few cases similar, often phase-like, changes were also noted in the blood content of noradrenaline and acetylcholine     

Effects of canine endotoxin shock on lymphocytic beta-adrenergic receptors

To determine whether beta-adrenergic receptors on circulating lymphocytes are impaired during endotoxemia and the precise role of catecholamines in this process, we allocated 16 dogs to three groups: I) control-saline vehicle (n = 5), II) endotoxin--Escherichia coli endotoxin 1.0 mg/kg iv bolus (n = 6), and III) endotoxin + propranolol--E. coli endotoxin 1.0 mg/kg after pretreatment with propranolol, 1.5 mg/kg iv bolus followed by a continuous infusion, 30 micrograms/kg per min, (n = 5). Five hours after endotoxin injection, lymphocytic beta-adrenergic receptor number and sodium fluoride (NaF)-stimulated cyclic AMP accumulation were reduced by 41 +/- 6% and 25 +/- 7% of baseline values, respectively, which were significantly different from those observed in the control group (both P less than .01). Propranolol pretreatment prevented the endotoxin-induced reduction in lymphocytic beta-adrenergic receptor number (P less than .02 compared with the endotoxin group), but not the decrease in NaF-stimulated cyclic AMP accumulation (P less than .01 compared with the control group). Myocardial beta-adrenergic receptor number was reduced in the endotoxin group compared with that observed in the control group (P less than .06). These changes were associated with a decreased chronotropic response to isoproterenol in the endotoxin group compared with the control group (P less than .05). We conclude that decreased lymphocytic beta-adrenergic receptor number in endotoxin shock is caused by circulating catecholamines, whereas alterations distal to the receptors may be due to other mechanisms.     

Hemodynamic evaluation of endotoxic shock in anesthetized piglets: antagonism of endogenous vasoactive substances

In anesthetized piglets the influence of an LD100 of Escherichia coli endotoxin (0.5 mg/kg IV, bolus injection) on several hemodynamic parameters and on survival time was studied. Endotoxin provoked a pronounced decrease in arterial pressure and cardiac output and an increase in portal venous and pulmonary arterial pressure and heart rate. Total peripheral and mesenteric vascular resistances displayed an initial increase followed by a sustained decrease, whereas pulmonary vascular resistance revealed a pronounced biphasic increase. All pigs died within 210 min following endotoxin administration. Pretreatment with the 5-HT2-antagonists R 41468 and R 50970 and with the prostanoid-synthesis inhibitor flurbiprofen induced a significant attenuation of the increase in pulmonary vascular resistance and beneficial effects on survival. Best survival results were obtained with prednisolone sodium succinate, although these results can only partly be ascribed to beneficial hemodynamic effects. The experiments with the opiate antagonists, however, point to detrimental effects.     

睡眠呼吸暂停低通气综合征患者血管活性物质的变化

目的 观察不同程度睡眠呼吸暂停低通气综合征(SAHS)患者血管活性物质内皮素-1(ET-1)、血管紧张素Ⅱ(AngⅡ)、血栓烷素B2(TXB_2)、6-酮-前列腺素F_(1α)(6-keto-PGF_(1α))、降钙素基因相关肽(CGRP)的变化及其相关性，旨在深入了解SAHS引起心血管病的机制，为有效防治SAHS患者的心血管并发病提供实验依据。资料与方法 疑似SAHS患者共37例，男32例，女5例，平均(55．70±10．66)岁，进行多导睡眠呼吸监测，记录呼吸暂停低通气指数(AHI)、呼吸紊乱指数(RDI)。根据RDI分为正常组，轻度SAHS组，中度SAHS和重度SAHS组。睡眠呼吸监测结束后即刻抽血，用放免法测定ET-1、AngⅡ、TXB_2、6-keto-PGF_(1α)、CGRP。结果 ①重度SAHS组的BMI显著大于正常及轻、中度组；②中、重度SAHS组ET-Ⅰ、AngⅡ、TXB_2水平显著高于正常组及轻、中度组，但四组6-keto-PGF_(1α)、CGRP水平均无统计学差异；③相关分析结果显示：AHI、RDI与ET-Ⅰ、AngⅡ、TXB_2水平显著正相关，6-keto-PGF_(1α)、CGRP水平则与SAHS参数无显著相关性。结论 体重指数与SAHS的发生发展密切相关，部分心血管活性物质如FF-Ⅰ，AngⅡ和TXB_2在SAHS引起的心血管疾病发生发展中发挥重要作用。     

新型KATP开放剂埃他卡林对低氧性肺动脉高压大鼠血管活性物质的影响

目的 探讨缺氧对大鼠血管活性物质分泌的影响及新型KATP开放剂埃他卡林(iptakalim, IPT)治疗肺动脉高压的作用机制. 方法 清洁级SD大鼠30只随机分成对照组、低氧组、IPT组,每组10只.将低氧组与IPT组放入常压低氧舱制备动物模型,采用右心导管测量大鼠肺动脉压,应用放射免疫法等观察血浆一氧化氮(NO)、内皮素-1(ET-1 )及前列环素(PGI2)水平的动态变化. 结果 低氧组大鼠肺动脉平均压显著高于对照组和IPT组(P＜0.05);低氧组大鼠血浆ET-1 含量升高,NO及PGI2含量降低,与对照组比较差异有统计学意义(P＜0.05);IPT能对抗缺氧引起的ET-1 含量升高和NO含量降低,与低氧组比较差异有统计学意义(P＜0.05);而对缺氧引起的PGI2含量降低则无明显影响. 结论 IPT能抑制缺氧引起的ET-1含量升高和NO含量降低,从而改善内皮细胞功能,降低肺动脉平均压.