Strain difference in pulmonary vascular responsiveness to hypoxia in rats

The difference in pulmonary vascular response to hypoxia between Hilltop Sprague-Dawley (HT) rats and Wistar (W) rats was studied. Effects of inhibitor of leukotriene (LT) synthesis or prostaglandin (PG) synthesis on hypoxic pulmonary vasoconstriction (HPV) and chronic pulmonary hypertension were observed, and variations in plasma TXB₂ and 6-keto-PGF_1a during hypoxia were determined. The results showed that in rats of both strains LTs are the major mediator of HPV, which is also mediated by vasoconstrictive PGs in HT rats, while modulated by vasodilative PGs in W rats. This might be the crucial mechanism responsible for the higher pulmonary vascular responsiveness in HT rats. Differences in the modulating effect of histamine and in the structural feature of pulmonary arteriole might be contributing factors as well.     

Relation of TXA2 and PGI2 to the difference in hypoxic pulmonary vasoconstriction between different strains of rats

TXB₂ and 6-keto-PGF₁ α levels in arterial and venous plasma of Wistar and Hilltop rats during hypoxia were measured to investigate the roles of TXA₂ and PGI₂ in hypoxic pulmonary vasoconstriction (HPV) and responsiveness difference of pulmonary vessels to hypoxia between different strains of rats. The results showed that PGI₂ might play an important role in maintaining the low resistance in pulmonary circulation of these two strains of rats. Increased TXA₂ during hypoxia may partially mediate HPV in Wistar rats, while augmented PGI₂ during hypoxia may modulate HPV in Wistar rats. This might be the important mechanism responsible for more intensive responsiveness of pulmonary vessels to hypoxia in Hilltop rats than in Wistar rats.     

先心病合并重度肺动脉高压围术期白细胞相关体液因素在肺损伤中的作用

为探讨白细胞相关体液因素在先天性心脏病(简称先心病)合并重度肺动脉高压围术期肺损伤中的作用机制,对31例先心病室间隔缺损(非肺动脉高压16例,重度肺动脉高压15例)行直视修补术患者的围术期肺动脉压、全肺阻力、血栓素B₂(TXB₂)、6-酮-前列腺素F₁α(6-keto-PGF₁α)、丙二醛(MDA)、白介素-8(IL-8)以及动脉血白细胞计数的变化进行了分组研究。结果显示,围术期TXB₂、6-keto-PGF₁α与TXB₂的比值(P/T)、MDA、IL-8、动脉血白细胞以及中性粒细胞计数的变化与围术期肺动脉压、全肺阻力的改变密切相关。提示在先心病合并重度肺动脉高压患者的围术期,白细胞引起的体液因素改变可以造成肺动脉高压患者的肺损伤,并影响其血流动力学。     

Effects of ligustrazine controlled release capsule in chronic pulmonary heart disease

Summary Before and after oral administration of ligustrazine controlled release capsule, pulmonary hemodynamics, right cardiac function, arterial blood gas and TXB₂/6-keto-PGF_1α were studied in 16 patients with advanced cor pulmonale. The decrease of pulmonary arterial pressure and pulmonary vascular resistance, increase of cardiac output, improvement of right cardiac function and arterial blood gas were demonstrated after one course of treatment. The mechanism of these effects may be related to improvement of imbalance of TXB₂/6-keto-PGF_1α. These results were in agreement with those of intravenous administration of ligustrazine, but no adverse reactions were found.     

Glioma prostaglandin levels correlate with brain edema

Summary The present study was designed to prospectively investigated the prostaglandin (PG) levels and extent of peritumoral edema in 30 cases of glioma by using methods of radioimmunoassay and imaging. Both TXB₂ and 6-keto-PGF₁₀ levels in all glioma groups went up over that in the control group. TXB₂ level and ratio of TXB₂/6-keto-PGF₁₀ were markedly increased with the extent of tumor malignancy. Water concentration in anaplastic astrocytoma and glioblastoma were significantly elevated. Difference in TXB₂ level and TXB₂/6-keto-PGF₁₀ ratio among three edema grades were statistically significant. TXB₂ level and ratio of TXB₂/6-keto-PGF₁₀ were closely correlated with water concentration (r₁ = 0. 53, r₂ = 0. 72,P <0. 01). Our findings suggested that the metabolism of PG in glioma were in the state of disorder, and that the imbalance between PGI₂ and TXA₂ may be one of factors which affect the formation of peritumoral edema.     

Factors Accounting for Different Responses of Pulmonary and Cerebral Vessels to Hypoxia

ＦａｃｔｏｒｓＡｃｃｏｕｎｔｉｎｇｆｏｒＤｉｆｆｅｒｅｎｔＲｅｓｐｏｎｓｅｓｏｆＰｕｌｍｏｎａｒｙａｎｄＣｅｒｅｂｒａｌＶｅｓｓｅｌｓｔｏＨｙｐｏｘｉａＷＡＮＧＤｉｘｕｎ（王迪浔），ＪＩＮＸｉａｎｒｏｎｇ（金咸瑢），ＬＩＵＳｈｅｎｇｙｕａｎ（刘声远）...     

烟酸对大鼠急性坏死性胰腺炎合并肺损伤的防治作用

采用牛磺胆酸钠诱发大鼠急性坏死性胰腺炎并发肺损伤模型,用放射免疫分析法动态测定大鼠血浆TXB₂、6-keto-PGF_1α质量浓度变化,并观察烟酸的防治作用.结果显示,急性坏死性胰腺炎组血浆TXB₂质量浓度升高,TXB₂/6-keto-PGF_1α显着升高,应用烟酸能明显降低TXB₂质量浓度,TXB₂/6-keto-PGF_1α比值显着降低,也降低了肺系数,改善肺组织病理形态变化.提示TXB₂、PGI₂平衡改变可能是急性坏死性胰腺炎并发肺损伤的病理机制之一,烟酸具有防治急性坏死性胰腺炎并发肺损伤的作用.     

Sympathetic innervation of pulmonary circulation and its role in hypoxic pulmonary vasoconstriction

The purposes of this study were to localize the position of spinal center of sympathetic nerve which controls the pulmonary circulation, and to evaluate the role of pulmonary sympathetic nerve in hypoxic pulmonary vasoconstriction (HPV) in pithed rat model. The sympathetic preganglionic fibers arising from C₇–T₁₀ segments were stimulated electrically in succession. During stimulation the pulmonary vascular resistance (PVR) was increased in all segments tested, most significantly in C₇-T₄ (about 28 % above control value), obviously higher than that in T₅-T₁₀. The higher the stimulated spinal segments, the larger the ratio of ΔPVR/ΔSVR. Alveolar hypoxia (12%O₂–88% N₂) could induce HPV in pithed rat. In the presence of hypoxia, stimulation of T₁–T₃ segments caused a double increment in PVR and -P_p, as compared with those during normoxia (P<0.05). The data show that 1) the spinal center of sympathetic nerve regulating the vasomotion of pulmonary circulation is located in the C₇-T₄ segments; 2) the excitation of sympathetic nervous system during hypoxia could enhance HPV.     

不同抗炎药物对缺氧所致大鼠离体肺血管环张力变化的影响

为研究离体大鼠肺血管在缺氧时张力的变化,以及甾体、非甾体类抗炎药物对此变化影响的异同性,采用等长收缩技术,测定加入消炎痛或地塞米松前后张力改变的特点及两药作用的差异。结果发现Wistar大鼠与Sprague-Dawley大鼠肺血管环对缺氧的反应不同,后者仅出现收缩反应,而Wistar大鼠在收缩前出现一内皮依赖的舒张;COX非特异性抑制剂消炎痛对缺氧所致的舒张和收缩均有增强作用;COX-2特异性抑制剂地塞米松则在明显抑制舒张的同时轻度增强收缩反应。结果表明不同种属大鼠的肺血管缺氧反应可能存在差异;缩管性PGs和扩管性PGs分别调节急性肺血管缺氧的舒张和收缩反应,这一过程呈一定的内皮依赖性;非选择性和选择性的COX抑制剂对肺血管缺氧反应的作用不尽相同。     

一氧化氮对急、慢性缺氧大鼠血流动力学及缺氧性肺血管收缩反应的影响

观察了吸入０．００４％的一氧化氮（ＮＯ）对急、慢性缺氧大鼠血流动力学、缺氧性肺血管收缩反应（ＨＰＶ）、血气及高铁血红蛋白（ＭｅｔＨｂ）的影响。结果表明：（１）常氧吸入ＮＯ时能明显降低慢性缺氧大鼠肺动脉平均压（Ｐｐａ）和肺血管阻力（ＰＶＲ），但对正常大鼠的Ｐｐａ和ＰＶＲ无明显影响；（２）慢性缺氧大鼠急性缺氧时ＨＰＶ较正常大鼠弱，吸入ＮＯ不但降低两者的急性缺氧肺动脉高压，且完全逆转两者的ＨＰＶ；（３）吸入ＮＯ对急、慢性缺氧大鼠体循环血流动力学、血气及ＭｅｔＨｂ含量无明显影响。提示吸入ＮＯ能选择性降低，急、慢性缺氧性肺动脉高血压，且逆转ＨＰＶ。     

Clinical observation on treatment of pediatric intractable nephropathy with modified Taohong Siwu decoction ()

Objective: To observe the clinical effect of Modified Taohong Siwu Decoction (MTSD) in treating pediatric intractable nephropathy (PIN).Methods: Ninety-five patients with PIN were divided into 2 groups at random. The 60 patients in the treated group were treated with MTSD and the 35 patients in the control group were treated with heparin. The clinical therapeutic effect and levels of thromboxane B₂(TXB₂) and 6-keto-prostacyclin F_la(6-keto-PGF_la) before and after treatment were observed. Results: The total effective rate in the treated group was 81.7%, which was similar to that in the control group (80.0%,P > 0.05). The levels of TXB₂ and TXB₂/6-keto-PGF_la ratio were higher in both groups of the patients as compared with those of the healthy control (P<0.01). After treatment, the two criteria were significantly improved in the two treated groups, as compared with those before treatment, the difference was significant (P<0.01), while in comparison between the MTSD treated group and the control group, no significant difference was found (P >0. 05).Conclusion: MTSD has good effect in treating PIN, it could improve the metabolic unbalance of thromboxane and prostacyclin.     

单肺通气期间肺损伤的机制及形态学研究

单肺通气(OLV)对肺组织的损伤主要有两方面机制,其一为缺氧性肺损伤,目前认为缺氧性肺血管收缩(HPV)是低氧对肺血管的直接作用,以及炎症性细胞因子释放的间接作用共同发挥效应;其二为机械的牵张性肺损伤,也用“生物性损伤”描述。现就近年来OLV所导致肺损伤的机制以及形态学变化作一综述。     

Effects of acute ingestion of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction in dogs—Role of leukotrienes

Summary The effects of acute intragastric administration of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction were studied in spontaneously breathing dogs. The dogs were given 0.5 g/kg of 10 % ethanol (v/v) in 5 min. Hemodynamic measurements were obtained before and 30 min after ingestion of ethanol. Mean pulmonary arterial pressure and pulmonary vascular resistance increased markedly after ingestion of ethanol, and hypoxic pulmonary vasoconstriction was augmented significantly by ethanol as well. Diethylcarbamazine citrate (DEC), a lipooxygenase inhibitor, inhibited these effects of ethanol in a dosage of 200 mg/kg. The above findings suggest that ethanol can induce pulmonary vasoconstriction, which may be predominantly mediated by leukotrienes (LTs).     

Effects of cigarette smoking on the function of metabolizing arachidonic acid and angiotensin I in the isolated perfused rat lungs

Summary The effects of acute and chronic cigarette smoking on the metabolism of exogenous arachidonic acid (AA) and angiotensin I (AI) in perfused isolated rat lungs were studied. The results showed that acute cigarette smoking did not alter the contents of 6-keto-PGF_1α (the stable metabolite of PGI₂) and TXB₂ (the stable metabolite of TXA₂) in the effluent and the increment of pulmonary artery pressure (†P_pa) caused by AA. The conversion of A I into A II was significantly increased (P<0.01), while the †P_{p a}, induced by A I injection was obviously decreased as compared with controls (P<0.05). After cigarette smoke exposure for 30 days, the †P_{p a} caused by AA or A I did, not differ from that of controls, but the contents of 6-ketoPGF_1α and A II increased more markedly than those in non-smoking rats,(P< 0.05). It is suggested that acute and chronic cigarette smoking in rats can promote the lung function of converting A I into A II, chronic smoking can increase the lung function of metabolizing AA into PGI₂.     

Clinical implication of the changes of cAMP,TXA<Subscript>2</Subscript> and PGI<Subscript>2</Subscript> in CSF of asphyxiated newborns

Summary To evaluate the changes of 3′, 5′-cyclic adenosine monophosphate (cAMP), thromboxane A₂(TXA₂) and prostacyclin (PGI₂) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischamic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB₂ (TXA₂ metabolite) and 6-keto-PGF_1α (PGI₂ metabolite) in CSF and plasma were measured 36–72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB₂ and 6-keto-PGF_1α). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60±2.40, significantly lower than that of the mild HIE group (14.83±2.84) and the control group (24.43±2.39) (for bothP<0.01). The levels of TXB₂ and 6-keto-PGF_1α in CFS in the moderate-severe HIE group (206.06±29.74, 168.47±23.02, respectively) were significantly higher than in the mild HIE group (83.37±28.57, 131.42±16.57, respectively,P<0.01) and the control group (41.77±21.58, 86.23±13.05, respectively,P<0.01). The level changes of cAMP, TXB₂ and 6-keto-PGF_1α in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P>0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79±13.34, 83.50±13.28, respectively), followed by mild HIE group (102.19±7.02, 99.94±9.08, respectively), with the control group being the highest (116.63±12.08, 116.69±10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group,P<0.01; the mild HIE group vs. the control groupP<0.05). The results suggested that the concentration of cAMP, TXA₂ and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome. LIU Hanchu, male, born in 1959, Associate Professor     

Study on therapeutic mechanism of Neiyifang in treating endometriosis

Objective: To observe the clinical effect of Neiyifang (NYF) in treating endometriosis and to explore its therapeutic mechanism through observing its influence on plasma β-endorphin (β-EP) in different menstrual stages and levels of prostaglandins (PGs) in menstruation.Methods:NYF was administered to 104 patients with endometriosis one dose daily with 3 successive menstrual cycles as one therapeutic course. Peripheral blood β-EP level in follicular, luteal and menstrual stages, as well as PGF_2α, PGE2, thromboxane B₂ and 6-keto-PGFl α levels in menstrual stage were detected by RIA, and controlled with those in 15 healthy persons.Results: (1) The total effective rate of NYF was 81.3% and it showed significant effect in improving patients’ clinical symptoms and physical signs; (2) In menstrual stage, the levels of β-EP, 6-keto-PGF_α/ TXB₂ were lower(P <0.05) and levels of PGF_2α, PGE₂, TXB₂ and 6-keto-PGF_1α were higher (P< 0. 05) in patients than those in control, and the higher the level of PGE₂, the severer the menalgia, (3) NYF could increase levels of β-EP, 6-keto-PGF_1α, and reduce levels of PGF_2α, PGE_2α in menstrual stage of patients (all P<0.05).Conclusion: (1) NYF has good clinical effect in treating endometriosis; (2) Patients’ symptom of menalgia is closely related with the excessive high levels of PGF_2α and PGE₂, PGI₂/TXA₂ ratio disturbance, and excessive low level of β-EP; (3) NYF could significantly decrease the PGE₂, PGF_1α levels, increase the 6-keto-PGF_1α/TXB₂ ratio and the level of β-EP, so as to alleviate the menalgia in patients with endometriosis. This item was supported by National Funds of Natural Sciences(No. 30070942)     

PI3K/Akt信号通路在缺氧性肺血管收缩中的机制

目的：探讨15-羟基二十碳四烯酸（15-HETE）致大鼠肺动脉收缩的信号转导途径,阐明15-HETE引起慢性缺氧性肺动脉收缩作用的可能机制。方法：采用组织浴槽血管环方法观察15-HETE对缺氧和正常组大鼠血管收缩的作用,同时观察PI3K/Akt抑制剂LY294002对肺动脉环收缩强度的改变,明确PI3K/Akt信号转导途径在15-HETE收缩肺动脉中的作用。结果：15-HETE对正常组和缺氧模型组大鼠血管环均有收缩作用,加入AKT抑制剂LY294002可明显阻断15-HETE对缺氧大鼠肺动脉的收缩作用（P〈0.05）。结论：15-HETE通过AKT信号转导途径收缩慢性缺氧性大鼠肺动脉。     

益智仁中二苯基庚烷类化合物的血管生成抑制活性

探讨益智仁中两个已知二苯基庚烷类化合物Yakuchinone A和Yakuchinone B以及结构类似物姜黄素(curcumin)的血管生成抑制活性。采用了转基因荧光斑马鱼为体内实验动物模型,人脐静脉内皮细胞(HUVEC)为体外实验模型,评价了上述3个化合物的活性及毒性。以血管生成抑制指数(AI)代表化合物的活性与毒性之比。结果表明,无论是体外实验还是体内实验,姜黄素的血管生成抑制作用最强而毒性最低,Yakuchinone A次之,Yakuchinone B抑制活性最低而毒性最强。因此,姜黄素为三者中最佳的血管生成抑制剂。     

Role of sympathetic nerve and adrenal gland in the potentiation of hypoxic pulmonary vasoconstriction during cigarette smoking

Summary The aim of this study was to investigate the role of sympathetic nerve and adrenal gland in the changes in hemodynamics and hypoxic pulmonary vasoconstriction (HPV) induced by cigarette smoking in Wistar rats. Data showed that an increment of pulmonary vascular resistance (PVR) induced by alveolar hypoxia was partially prevented by prazosin (α₁-receptor blocker) and prazosin combined with propranolol (β-receptor blocker), but not significantly affected by propranolol or adrenalectomy. Cigarette smoking tould increase PVR and potentiate HPV, whereas the potentiation of HPV was partially inhibited by prazosin and strengthened by propranolol, but not affected by adrenalectomy. It is suggested that the sympathetic nerve excitation caused by cigarette smoking may play a role in the strengthening of HPV.     

Protective effects of effective ingredients of Danshen (Radix Salviae Miltiorrhizae) and Honghua (Flos Carthami) compatibility after rat hippocampal neurons induced by hypoxia injury

OBJECTIVE

To investigate the effective ingredients of Danshen (Radix Salviae Miltiorrhizae) and Honghua (Flos Carthami) (Danhong) on protective properties towards neonatal rat hippocampal neurons under hypoxia condition.