缩宫素对大鼠心肌缺血再灌注后一氧化氮及内皮素-1的影响

目的探讨缩宫素(OT)对大鼠急性心肌缺血再灌注后一氧化氮(NO)与内皮素-1(ET-1)的影响及可能的机制。方法将大鼠随机分为心肌缺血再灌注组(I/R组)、I/R+OT预处理组(I/R+OT组)、假手术组(SH组)和健康对照组(N组)。采用在体大鼠结扎冠状动脉前降支25min后,松扎再灌注120min形成I/R模型,SH组只穿线不结扎。I/R+OT组在缺血前25min腹腔注射OT 0.03μg/kg,其余3组给予等量生理盐水。再灌注结束后测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、NO及ET-1;再灌注结束时,采用HE染色进行心肌组织形态学分析。结果光镜下观察,N组与SH组心肌细胞排列整齐,无肌纤维破坏,I/R组心肌纤维排列不规则、断裂,心肌间质水肿,较多粒细胞灶状浸润,I/R+OT组可见心肌细胞排列、间质水肿及粒细胞浸润程度介于N组与SH组。与SH组相比,I/R组和I/R+OT组血清CK-MB、LDH、ET-1升高,NO水平降低,差异均有统计学意义(P均<0.05),而N组的表达差异无统计学意义(P>0.05);与I/R组相比,I/R+OT组血清CK-MB、LDH、ET-1降低,NO水平升高,差异均有统计学意义(P均<0.05)。I/R组和I/R+OT组血清NO与ET-1水平呈负相关(P<0.05)。结论 OT预处理对大鼠I/R有保护作用,其作用机制可能与OT增加血清NO水平、降低ET-1水平有关。

Total synthesis of endothelin 1 by microwave-assisted solid phase method

A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The whole peptide was cleaved from the resin and two disulphide bridges were formed under air oxidation at room temperature.The purity and efficiency of synthesizing the peptide is much higher than other methods used before.

Study on Changes of Plasma Endothelin-1 in Sheep with Experimental Colonic Obstruction

The present study was designed to determine the relationship between changes of plasma endothelin 1 concentrations and development of colonic obstruction in sleep.Colons were bound in three sheep with sterilized plastic tubes to make pathological model of colonic obstruction.Samples were collected before and after modeling operation on both controls and models.Endothelin 1 concentrations were measured by radioimmunoassay.Plasma ET llevels decreased continually after the modeling operation in the models,it dropped from a basal value of 60 93±18 66 to 34 11±8 22 and 33 54±11 12 pg/mL(P<0 05) on the 3rd and 5 th day,respectively,which were also lower than controls 64 16±12 93 pg/mL(P<0 05).It suggests that colonic obstruction may induce a decrease in plasma endothelin 1 concentrations in sleep.

The Releasing Effects of Captopril and Sodiun Nitroprusside on Endothelin-1 in Vascular Smooth Muscle Cell

Objective To investigate the influence of captoprial and SNP on the release of ET -1 in cultured VSMC of rats. Methods Measurement of endothelin - 1 levels by radioimmljnoassay in various concentrations of captopril and/or sodium nitroprusside in cultured vascular smooth muscle cell (VSMC) of rats. Results Both captopril and SNP could reduce the high ET - 1 levels of VSMC which were caused by Ang Ⅱ. There was a linear relationship between Ang Ⅱlevels and ET -1 production ( r = 0. 760, P <0. 001 ) . Conclusion Endothelin - 1 may accelerate the formation and development of atherosclerosis through inhibiting endogenous NO production by VSMC. ACEI or NO inhibition of ET -1 release could reduce atherosclerosis formation.

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

The Role of Neutrophil Activation in Pathogenesis of Preeclampsia

To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin 1 (ET 1) and serum NO - 2 were also measured by using non equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38±179.91 and 326.97±170.14 respectively ( P < 0.05). The plasma ET 1 level and serum NO 2 concentration in pre eclampsic women (63.69±48.33 pg/ml and 20.03±4.77 μmol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98±20.25 pg/ml and 15.47±5.47 μmol/L, respectively, P <0.01). The neutrophil CD11b expression was significantly elevated in pre eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre eclampsia.

Effects of endothelin B receptor antagonists, BQ788 and ET-1_(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

Objective To explore the role of endothelin (ET) in the pathogenesis of exercise induced asthma (EIA), we investigated the effects of ET B receptor antagonists, ET 1 11 21 fragment and N cis 2,6 dimethylpi^peridinocardonyl L γ methylleucyl D 1 methoxycarbonyl tryptophanyl D norleucine (BQ788) on broncho^constriction elicited by isocapnic hyperpnea in guinea pigs Methods Eighteen pathogen free Hartley guinea pigs were randomly divided into three groups A: normal saline (NS) inhalation control group (n=6), B: BQ788 group (n=6), and C: ET 1 11 21 fragment group (n=6) Guinea pigs were anesthetized with pentobarbital sodium After measuring the basal value of lung resistance (R L) and dynamic compliance of the respiratory system (Cdyn), NS (0 96?ml), BQ788 (9?nmol) and ET 1 11 21 fragment (9?nmol) were inhaled A rodent respirator with a dry 5%CO 2-95%O 2 mixture at room temperature provided mechanical ventilation (V T 8?ml/animal, 100 breaths/min) for 5?min R L and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in R L and decrease in Cdyn R L and Cdyn of the guinea pigs from BQ788 group and ET 1 11 21 fragment group did not change significantly Conclusion It was demonstrated that selective ET B receptor antagonists, ET 1 11 21 fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors It was suggested that ET receptor antagonists, especially ET B receptor antagonist, might be beneficial in preventing EIA

Is endothelin-1 an aggravating factor in the development of acute pancreatitis?

Objective We have reported previously that ceruleininduced edematous pancreatitis would transform into hemorrhagic pancreatitis by administration of endothelin1 in rats In the present study, we tried to protect rat model from developing into hemorrhagic pancreatitis with BQ123 (an ETA receptor ant agonist) Methods The rat model was made by 5hour restraint waterimmersion st ress and two intraperitoneal injections of cerulein (40?g/kg) at hourly inter val BQ123 (3 or 6?mg/kg) was administered intravenously 30 minutes befo re and 2 hours after the first cerulein injection Results Acute hemorrhagic pancreatitis was induced in all rats treated with cerulin+stress The score for pancreatic hemorrhage was 2402 in this g roup In the rats pretreated with BQ123, the score was reduced to 100 0, p ancreas wet weight and serum amylase activity were significantly reduced, and hi stologic alterations in the pancreas lightened, also the local pancreatic blood flow improved without affecting the systemic blood pressure Conclusions These results suggest that endothelin1 should play a role in aggravating the development of acute hemorrhagic pancreatitis, through its a ction on the pancreatic microcirculation

Modified cold storage of rat livers with self-made HYD solution

Objective To investigate the cold preservation effect on rat livers of a modified storage method with self-made HYD solution.Methods The vascular bed of rat livers was expanded with an additional 20 to 40?ml self-made HYD solution/100?g liver. After resection of the liver, the extra HYD solution (expressed as % liver weight) was entrapped via portal infusion by tying off the supra- and infra-hepatic inferior vena cava. Forty rats were randomly divided into four groups including control group with conventional storage method, and 20%, 30% and 40% groups according to the amount of extra HYD solution. We compared the preservation effect of the modified storage method with that of the conventional storage method using an isolated perfused rat liver model.Results Bile production and all the indices of hepatic microcirculation including portal perfusion pressure, endothelin-1 in the effluent, trypan blue distribution time and histology were significantly superior in the modified method groups compared to those in the control group (P<0.05). The contents of dihydroxybenzoic acid (DHBA) in the modified method groups were significantly lower than those in the control group (P<0.05). Liver enzymes activities in the 30% group were markedly lower than those in the control group (P<0.05). The preservation effect on rat liver in the 30% group was the best among the modified method groups.Conclusion The modified cold storage method is effective and may have potential for clinical application in liver preservation.