Mechanism of overproduction of plasma prostacyclin in portal hypertensive rats

OBJECTIVE: To evaluate the role of increased portal pressure and portosystemic shunting in elevated level of prostacyclin (PGI2) in portal hypertension. METHODS: Thirty-six male Sprague-Dawley rats were divided into four groups: prehepatic portal hypertension (PHPH, 8 rats), intrahepatic portal hypertension (IHPH, 9), end-to-side portacaval shunt (PCS, 8), and sham-operated controls (SO, 11). Two weeks after surgery, free portal pressure (FPP) was measured; systemic and splanchnic hemodynamics was studied by radioactive microsphere technique and blood sample from the femoral artery was obtained to measure the level of plasma 6-keto-PGF1 alpha with radioimmunoassay. RESULTS: The FPP (mmHg) in IHPH, PHPH, PCS and SO rats was 13.10 +/- 1.02, 12.10 +/- 1.52, 3.0 +/- 0.82 and 6.86 +/- 0.69, respectively. The value of FPP was significantly increased in IHPH, PHPH rats and significantly decreased in PCS rats when compared to SO rats. Cardiac index (CI) and portal venous inflow (PVI) were in the order of PCS > PHPH > IHPH > SO rats. Portosystemic shunting (PSS) in PCS, PHPH, IHPH was 99.7 +/- 0.29%, 76.02 +/- 20.62% and 30.34 +/- 10.18%, respectively. The concentrations of plasma 6-keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS and SO rats were 6.93 +/- 2.43, 5.09 +/- 2.27, 2.36 +/- 1.01 and 1.56 +/- 0.61, respectively. The concentrations of plasma PGI2 in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Furthermore, the concentrations of plasma PGI2 in PHPH and IHPH rats were also significantly higher than those in PCS rats. Moreover, a closed positive correlation existed between plasma PGI2 and FPP (r = 0.67, P < 0.001). CONCLUSIONS: The results of the present study suggest that the elevated PGI2 in portal hypertension is mainly due to the overproduction of PGI2 in vascular epithelium cells induced by increased portal pressure, whereas portosystemic shunting and liver dysfunction play a secondary role. In addition, the results of this study do not support that PGI2 mediated the hyperhemodynamics in portal hypertension.     

环氧化酶抑制剂对门高压大鼠一氧化氮合酶表达的影响

目的探讨一氧化氮合酶和前列环素在门静脉高压症高动力循环中的作用。方法选取96只SD大鼠,随机分为三组:肝内型门脉高压组(n=31)、肝前型门脉高压组(n=33)和手术对照组(n=32)。短期和长期应用环氧化酶抑制剂吲哚美辛后,分别测定三组大鼠门静脉压力以及血浆前列环素和一氧化氮浓度变化,并通过分光光度法和逆转录-聚合酶链反应法分别检测各组大鼠组织中一氧化氮合酶活性和mRNA表达。结果与短期相比,长期应用环氧化酶抑制剂后,门静脉压力和一氧化氮浓度显著升高(P<0.05),与持续下降的血浆前列环素浓度相反;同时内脏和血管组织诱导型一氧化氮合酶基因表达和活性均伴有显著增加(P<0.05),但组成型一氧化氮合酶基因表达和活性无显著变化(P>0.05)。结论诱导型一氧化氮合酶引起的一氧化氮过度合成和释放可能是导致门静脉高压症高动力循环的重要相关因素,一氧化氮和前列环素之间可能存在相互作用,而前列环素可能并不参与门静脉高压症高动力循环的维持和发展。     

The role of vasoactive substances in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

Objective To evaluate the role of endogenous vasoactive substances in hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats. Methods Male SD rats were randomly divided into 4 groups: normal controls (NL, n=10), rats with intrahepatic portal hypertension (IHPH, n=10), normal rats with OLT (NL-OLT, n=9), and IHPH rats with OLT (IHPH-OLT, n=16). IHPH-OLT rats were divided into 2 subgroups: Group A (3 days after OLT, n=9) and Group B (7 days after OLT, n=7). IHPH was induced by injection of CCI(4) and OLT was performed using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Radioactive microsphere method was used for hemodynamic study. The concentrations of plasma glucagon (Glu), nitric oxide (NO), prostaglandin (PGI(2)), thromboxaneA(2) (TXA(2)) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference in hemodynamic changes was observed between NL-OLT and NL rats, except for mean arterial blood pressure. No significant changes in NO and PGI(2) were seen between NL-OLT and NL rats. Glu, ET and TXA(2) were significantly elevated in NL-OLT rats compared with NL rats (P&lt;0.05). Characteristics of systemic and splanchnic hyperdynamic circulatory states were observed in IHPH, IHPH-OLT A, IHPH-OLT B rats. Both the magnitude of hyperhemodynamics and increasing concentrations of Glu and NO occurred in the order of IHPH&gt;IHPH-OLT A&gt;IHPH-OLT B rats. The level of plasma PGI(2) in IHPH rats was significantly elevated compared with NL rats, while PGI(2) in IHPH-OLT A and B rats was found to be lower than in IHPH rats (P&lt;0.05). There was no obvious difference in PGI(2) between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA(2) were found elevated in IHPH-OLT rats. Conclusions OLT does not induce postoperative hyperhemodynamics per se. Vasodilators including NO and Glu, especially NO, play an important role in the hyperhemodynamics of IHPH and IHPH-OLT rats. The results of the present study demonstrate that the persistence of systemic and splanchnic hyperkinetic circulation in the early stages after OLT may result from those non-eliminated factors that caused hyperhemodynamics in liver cirrhosis patients with portal hypertension before OLT.     

Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats

Ｐｒｅｖｉｏｕｓｓｔｕｄｉｅｓｈａｖｅｓｈｏｗｎｔｈａｔｓｙｓｔｅｍｉｃａｎｄｓｐｌａｎｃｈｎｉｃｈｅｍｏｄｙｎａｍｉｃａｂｎｏｒｍａｌｉｔｉｅｓｐｅｒｓｉｓｔｉｎｃｉｒｒｈｏｔｉｃｐａｔｉｅｎｔｓｗｉｔｈｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｏｎａｆｔｅｒｏｒｔｈｏｔｏｐｉｃｌｉｖｅｒｔｒａｎｓｐｌａｎｔａｔｉｏｎ(ＯＬＴ),ｄｅｓｐｉｔｅｔｈｅｒｅｔｕｒｎｏｆｐｏｒｔａｌｐｒｅｓｓｕｒｅｔｏｎｏｒｍａｌＴｈｅｅｌｕｃｉｄａｔｉｏｎｏｆｔｈｅｍｅｃｈａｎｉｓｍｒｅｍａｉｎｓｃｏｎｔｒｏｖｅｒｓｉａｌ15…     

Effects of hepatotrophic factors on the liver after portacaval shunt in rats with portal hypertension

Background Portacaval shunt （PCS） prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt. Methods Intrahepatic portal hypertension （IHPH） was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model （IHPH group）. Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups： normal saline （NS） given to 8 rats, hepatocyte growth factor （HGF） 8, insulin （INS） 8, hepatocyte growth factor and insulin （HGF＋INS） 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter. Portal venous pressure （PVP） was measured. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were tested biochemically and those of hyaluronic acid （HA） and laminin （LN） were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type I and In were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS 10.0. Results PVP was significantly higher in the IHPH rats than in the control rats （P〈0.05）. The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type I and III increased more significantly in the IHPH group than in the control rats （P〈0.05）. The number of mitochondria decreased more significantly in the IHPH rats than in the control rats （P〈0.05）. The levels of serum ALT, AST, HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the amount of collagens type I and M in the HGF and HGF＋INS rats were significantly lower than those in the NS rats （P〈0.05）. The damage to hepatocyte ultrastructure was markedly alleviated and the number of mitochondria was increased more significantly in the HGF and HGF＋INS rats than in the NS rats under an electron microscope. Conclusions Perfusion of exogenous hepatotrophic factors through the portal vein can alleviate liver injury, minimize the damage to the ultrastructure of hepatocyte, protect liver function, and lessen hepatic fibrosis in rats with portal hypertension after PCS.     

一氧化氮在肝前性门静脉高压症形成中的作用

目的：了解一氧化氮（NO）在肝前性门静脉高压症形成中的作用。方法：部分门静脉结扎（PVL）法制备肝前性门静脉高压症大鼠模型，以硝酸还原酶和比色法检测正常组，假手术（SO）组及PVL组术后不同时间点的门静脉血浆NO、一氧化氮合酶（NOS）水平，观察其血流动力学指标的动态变化及NOS抑制剂硝基－L－精氨酸甲酯(L-NAME)对门静脉高压大鼠血流动力学的影响。结果：SO组各时间点与正常组比较，NO，NOS及血流动力学指标均无显性差异，PVL组术后各时间点与正常组比较，NO，NOS，门静脉压力（PVP），门静脉阻力（PVR）明显升高（P＜0．05），平均动脉压（MAP），内脏血管阻力（SVR）明显降低（P＜0．05），门静脉血流量（PVF）无显性差异，且血浆NO水平与PVP，PVF，SVR，MAP呈显相关性，NAME能使门静脉高压大鼠PVP，PVR显下降（P＜0．05），使SVR，MAP显上升（P＜0．05）。结论：门静脉高压症大鼠存在高动力循环状态；NO参与了PVL术后血流动力学的变化及肝前性门静脉高压症模型的形成。     

PGI2,TXA2与先兆早产的关系研究

为探讨前列环酸（ＰＧＩ２）和血栓素（ＴＸＡ２）与先兆早产的关系，采用放射免疫法分别测定了先兆早产和足月临产孕妇血及宫颈粘液中６－酮－ＰＧＦ１α、ＴＸＢ２和孕酮的浓度，并与相对应孕周的孕妇进行比较。结果：与对照组相比，先兆早产组及足月临产组的血浆ＴＸＢ２和６－酮－ＰＧＦ１α水平明显升高（Ｐ〈０．００１），６－酮－ＰＧＦ１α／ＴＸＢ２比值降低（Ｐ〈０．００１），而孕酮水平则无显著性差异（Ｐ〉０．０５）     

DYNAMIC OBSERVATION ON THE CHANGES OF PLASMA SOMATOSTATIN AND GLUCAGON DURING THE DEVELOPMENT OF CIRRHOSIS AND AFTER PORTACAVAL SHUNTING IN THE CIRRHOTIC RATS

In the present study we observed dynamically and systemically the changes of plasma somatostatin and glucagon in the peripheral and portal vein, and the changes of pancreatic immunopathology in the course of development of cirrhosis induced by CCl_4 and after portacaval shunt (PCS) in the cirrhotic rats as well as investigated their causes and correlationship. The results showed that hyperglucagonemia was caused by spontaneous portosystemic shunting and surgically induced portacaval anastomosis. Moreover, there was much higher level of glucagon in the portal vein with corresponding increase of A cells in PCS rats than those in the controls, indicating that another cause for elevation of glucagon was hypersecretion of pancreatic A cells. Our data demonstrated that both deterioration of liver function and portosystemic shunting might not be responsible for the elevated level of somatostatin in the cirrhotic rats with PCS. However, there was a closed positive correlation between plasma glucagon and somatostatin. Thus it was concluded that hyperglucagonemia stimulated the release of somatostatin. In view of the fact the elevated level of glucagon was much higher than that of somatostatin, there was probably a relative lack of somatostatin in cirrhosis with portal hypertension.     

不同术式对肝硬变门脉高压大鼠胃粘膜血流量的影响

通过动物实验观察了门奇断流术，门腔分流术，远端脾腔分流术对门脉高压大鼠胃粘膜血流量的影响。结果表明，肝硬变门脉高压时，虽然整体胃血流处于高动力状态，而粘膜却明显缺血，从而造成粘膜抵抗力降低，构成了粘膜缺血及病变，可能是断流术后再出血率高的原因之一；ＰＣＳ术则明显改善了粘膜微循环；ＤＳＣＳ选择性改善了胃底部粘膜微循环，提高 膜抗病能力。     

An animal study of portal hypertension

For the purpose of elucidation the mechanism of portal venous resistance and portal venous blood flow in maintaining an elevated portal hypertension. The splanchnic and systemic hemodynamics were evaluated in portal hypertensive rat model, which is induced by partial portal vein ligation (PVL). Organ blood flow and portal-systemic shunting were measured by radio-active microsphere techniques. In this study all the PVL rats had higher mean portal venous pressure (15.2 +/- 1.6 mmHg) when compared to the Sham-operation control rats (5.3 +/- 1.2 mmHg). Furthermore, portal systemic shunting was significantly higher in the 14th day PVL rats (87.2 +/- 3.6%) than control rats (0.3 +/- 0.1%) (p less than 0.05). There was a rapid increase in portal venous inflow from the 4th day (6.1 +/- 0.8 vs 4.2 +/- 0.7 ml/min/100 gm BW, p less than 0.05) in the PVL rats than in control rats. However, the total peripheral resistance and splanchnic arterial resistance were reduced in the 14th PVL rats than control rats. The Cardiac index was much higher in the 14th PVL rats than control rats. Thus our results demonstrate that portal hypertension is maintained by a hyperdynamic portal venous inflow. This model is reproducible for us to study portal hypertension within a short period of time.     

Clinical Implication of the Changes of cAMP, TXA_2 and PGI_2 in CSF of Asphyxiated Newborns

Summary:To evaluate the changes of 3',5'-cyclic adenosine monophosphate(cAMP),thromboxane A_2(TXA_2)and prostacyclin(PGI_2)in cerebrospinal fluid(CSF)in the asphyxiated newborn andexplore their roles in hypoxic-ischamic brain damage(HIBD).Thirty-six full term newborns were di-vided into 3 groups,including 12 with moderate-severe hypoxic-ischaemic encephalopathy(HIE),13with mild HIE,11 without HIE(control group).The levels of cAMP,TXB_2(TXA_2 metabolite)and6-keto-PGF_(1α)(PGI_2 metabolite)in CSF and plasma were measured 36—72h after birth by RIA.andthe concentrations were expressed as nM/L(cAMP),ng/L(TXB_2 and 6-keto-PGF_(1α)).The infantswere followed-up at 6 and 12 month of age and Mental Development Index(MDI)and PsychomotorDevelopment Index(PDI)were measured using Bayley Scales of Infant Development(BSID).TheCSF cAMP level in moderate-severe HIE group was 8.60±2.40,significantly lower than that of themild HIE group(14.83±2.84)and the control group(24.43±2.39)(for both P<0.01).The lev-els of TXB_     

二氢睾酮和其受体对雄性大鼠血小板激活、TXA2／PGI2平衡与细胞内钙离子浓度的调节

目的研究生理剂量二氢睾酮（dmydrotestosferone，DHT）和其受体对雄性大鼠血小板激活、TXA2／PGI2平衡与细胞内钙离子浓度的调节。方法血浆睾酮（testosterone，T）应用Advia Centaur免疫检测系统测定（Bayer，Ger-many），血浆DHT应用酶联免疫试剂盒（ELISA kit）推荐方法检测。应用血小板聚集仪测定血小板聚集、血小板黏附仪测定血小板黏附。应用放免法测定TXB2和6-Keto—PGF1α。应用流式细胞仪测定血小板内钙离子浓度。结果去势雄性大鼠每日补充DHT（0．25mg／rat）使其DHT浓度达到生理水平，而且与氟他胺（flutamide）（每两日注射1次5mg／rat）联用不影响DHT浓度达到生理水平。DHT（2nM）显著抑制二磷酸腺苷（adenosine diphosphate，ADP）诱导的血小板的聚集、黏附。氟他胺预处理血小板之后，ADP诱导的血小板的聚集、黏附再次增加。去势雄性大鼠每日补充DHT（0．25mg／rat）降低TXB2和6-keto-PGF1α。的比例，然而两日补充一次氟他胺（5mg／rat）再次增加TXB2和6-keto-PGF1α。的比例。DHT（2nM）明显降低ADP诱导的血小板内钙离子浓度。然而，氟他胺预处理血小板之后ADP诱导的血小板内钙离子浓度再次增加。结论生理水平二氢睾酮介导其受体调节雄性大鼠ADP诱导的血小板聚集、黏附与其调节TXA2／PGI2平衡和血小板内钙离子浓度有关。     

血红素氧化酶在门静脉高压大鼠肝脏和小肠中的表达

观察血红素氧化酶（HO）异构酶在门静脉高压组和假手术组大鼠肝脏和小肠中的表达。用免疫组化方法检测HO蛋白在肝脏、小肠和脾脏中的表达。原位杂交方法检测HO－1 mRNA在肝脏中的表达。发现假手术组：HO－2在肝细胞内呈弥漫性表达，在枯否细胞和星状细胞内也有表达，在脾脏红髓的窦内皮细胞和小肠浆膜层、肌层中也呈弥漫性表达，而HO－1仅在肝脏的枯否细胞中表达，肝细胞中无表达，脾脏和小肠中的表达与HO－2表达相同。门静脉高压组：HO－2在肝脏和内脏中表达无明显变化，HO－1在肝脏中弥漫性表达，呈现上调，小肠中的表达也呈现上调。结果表明：在正常时，HO－2蛋白主要由肝细胞产生，门静脉高压时，肝脏HO－1表达上调，其产生的一氧化碳（CO）可能在高动力循环状态下对血管张力起一定的调节作用。     

Prostacyclin and thromboxane in diabetes

Concentrations of the stable antiaggregatory prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and of the proaggregatory thromboxane A2 metabolite thromboxane B2 were measured by radioimmunoassay in plasma from 53 diabetics. In 33 of these patients the ability of platelets to produce thromboxane B2 during spontaneous clotting was also studied. Plasma 6-keto-PGF1 alpha concentrations were higher (p less than 0.05) in the diabetics (mean 107.7 +/- SE 7.6 ng/l) than in non-diabetic controls matched for age and sex (87.5 +/- 4.7 ng/l), and diabetics with microangiography (n = 28) and higher (p less than 0.01) concentrations (124.3 +/- 10.8 ng/l) than those without microangiography (n = 25; 89.2 +/- 9.3 ng/l). Plasma thromboxane B2 concentrations were also higher (p less than 0.01) in the diabetics (mean 218.5 +/- SE 25.3 ng/l) than in the controls (127.7 +/- 9.8 ng/l), but this increase was not related to microangiography. The ability of platelets to generate thromboxane B2 did not differ between the diabetics (181.4 +/- 16.4 microgram/l) and controls (195.8 +/- 11.8 microgram/l). Platelets of diabetics with microangiopathy or taking oral hypoglycaemic agents (n = 19), however, produced decreased amounts of thromboxane B2 during clotting. Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 were not related to concentrations of glucose, haemoglobin A1, high-density lipoprotein cholesterol, cholesterol, triglycerides, magnesium, or creatinine. These results suggest that in diabetics with microangiopathy a balance between prostacyclin and thromboxane A2 is shifted to dominance by prostacyclin.     

高效液相色谱-质谱法检测Wistar大鼠主动脉6-keto-PGF_（1α）的生成

目的：建立大鼠主动脉6-keto-PGF1α的高效液相色谱-质谱（HPLC-MS）检测方法,以反映前列环素（PGI2）的产生水平。方法：建立用HPLC-MS同时检测环氧化酶（COX）代谢通路的5种前列腺素类产物的方法和Wistar大鼠主动脉产生的6-keto-PGF1α水平。结果：HPLC-MS检测法能同时检测COX代谢通路的5种PGI2产物和大鼠主动脉产生的6-keto-PGF1α;加入内皮受体激动剂乙酰胆碱后6-keto-PGF1α的生成明显升高。结论：成功建立用HPLC-MS检测Wistar大鼠主动脉所生成6-keto-PGF1α的方法。     

缬沙坦和吲哒啪胺对高血压病患者细胞因子影响的对比研究

目的:比较吲达帕胺和缬沙坦治疗对高血压病患者外周血中细胞因子单核细胞趋化因子-1(MCP-1)、巨噬细胞炎性蛋白1α(MIP-1α)、可溶性P选择素(sP-selectin)、非对称二甲基精氨酸(ADMA)、血管紧张素Ⅱ(AngⅡ)和6-酮-PGF1α(6-keto-PGF1α)的影响。方法:选取我院门诊健康体检者20例和41例原发性高血压患者,将41例高血压患者随机分为吲哒啪胺组(20例)和缬沙坦组(21例),分别予吲哒啪胺(商品名钠催离)1.5mg/d和缬沙坦(商品名代文)80mg/d治疗4周,治疗前和治疗4周后抽血检测MCP-1,MIP-1α,sP-selectin,ADMA,AngⅡ和6-keto-PGF1α含量。结果:同正常血压组相比,高血压病患者外周血中MCP-1,MIP-1α,sP-selectin,ADMA浓度显著增加。吲哒啪胺组治疗前后MCP-1,MIP-1α和sP-selectin浓度无明显变化;而缬沙坦治疗4周后,MCP-1,MIP-1α和sP-selectin浓度与治疗前相比均显著下降分别为(19.16±3.11)pg/mLvs(16.08±2.67)pg/mL,P<0.05;(27.74±8.36)pg/mLvs(17.64±7.59)pg/mL,P<0.05;(2.67±3.18)pg/mLvs(6.15±2.94)pg/mL,P<0.01。吲达帕胺和缬沙坦治疗后,ADMA浓度均下降分别为(1.35±0.74)μmol/Lvs(0.98±0.56)μmol/L,P<0.05;(1.31±0.68)μmol/Lvs(0.71±0.52)μmol/L,P<0.01,而6-keto-PGF1α浓度增加,但在缬沙坦组增高更加显著分别为(61.96±20.81)pg/mLvs(96.72±25.89)pg/mL,P<0.05;(63.25±16.92)pg/mLvs(143.22±43.45)pg/mL,P<0.01。两组治疗前后AngⅡ无显著变化。结论:轻中度高血压病患者外周血中细胞因子MCP-1,MIP-1α,sP-selectin和ADMA的浓度增加;缬沙坦和吲哒啪胺具有相似的降压疗效,同时还可降低上述细胞因子水平。     

热休克蛋白90在门脉高压大鼠内脏高动力循环中的作用

目的研究热休克蛋白90(HSP90)在门脉高压大鼠内脏高动力循环中的作用。方法20只SD大鼠制成门脉高压动物模型,10只大鼠行假手术作为对照。4周后处死动物获取肠系膜动脉。测定其对甲氧胺(MTX)和乙酰胆碱的量效曲线。然后再灌注格尔德霉素(GA),再次测量其量效曲线。去内膜后,再测量肠系膜动脉对硝普钠(SNP)的量效曲线。结果肠系膜动脉对MTX的反应性降低。而GA能增强门脉高压大鼠肠系膜血管对MTX的反应性。GA还能减少肠系膜血管乙酰胆碱依赖的血管扩张,但不能减少SNP依赖的血管扩张。结论本研究说明了HSP90在门脉高压大鼠内脏高动力循环中起重要作用。     

Effects of acupuncture on the levels of endothelin, TXB2, and 6-keto-PGF1 alpha in apoplexy patients.

In order to delve into the mechanism governing the treatment of apoplexy by acupuncture at yangming channel points as main points, we observed the changes in the endothelin (ET) level in plasma, TXB2 and 6-Keto-PGF1 alpha levels in urine in convalescent apoplexy patients during acupuncture treatment. The results showed that the ET level in plasma in convalescent apoplexy patients was significantly higher than that in healthy subjects (P < 0.05), and the ET level in plasma in patients was decreased after one course of acupuncture treatment. It was found that before treatment the TXB2 level in urine in apoplexy patients was significantly higher than in healthy subjects, and the 6-Keto-PGF1 alpha level in urine in the patients was significantly lower than that in healthy subjects, with an increased ratio of TXB2 to 6-Keto-PGF1 alpha. After acupuncture treatment, the TXB2 level in urine was lowered with a decrease in the ratio of TXB2 to 6-Keto-PGF1 alpha. All this indicated that one of the mechanisms governing acupuncture treatment of apoplexy acupuncture at yangming channel points as main points was that acupuncture could produce therapeutic effects by adjusting the imbalance of important vaso-active substances, ET, TXA2, and PGI2.     

门腔分流术后经门静脉输入肝营养因子对肝功能的保护作用

目的 观察肝硬变、门静脉高压症大鼠接受门腔分流手术后,经门静脉输入肝营养因子(促肝细胞生长素、胰岛素)对肝脏功能、病理改变及纤维化程度的影响.方法 肝硬化门静脉高压大鼠随机数字表法分人正常对照组、肝硬变模型组、生理盐水(NS)治疗对照组、促肝细胞生长素(HGF)治疗组、胰岛素(INS)治疗组、促肝细胞生长素+胰岛素(HGF+INS)治疗组.各治疗组大鼠行门腔静脉端侧分流术后给予相应肝细胞营养因子,治疗结束时,取血测定肝功能,取肝组织进行肝硬化分级.结果 血清丙氨酸转氨酶(ALT):HGF治疗组(42.0±9.5)U/L、HGF+INS治疗组(30.1±4.1)U/L明显低于NS组(56.5±12.4)U/L;天门冬氨酸转氨酶(AST):HGF治疗组(172.9±42.8)U/L、HGF+INS治疗组(133.7±21.2)U/L明显低于NS组(266.9±81.5)U/L;血清透明质酸(HA):HGF治疗组(435.4±127.7)μg/L、HGF+INS治疗组(322.5±52.3)μg/L明显低于NS组(563.0±146.4)μg/L,层粘连蛋白(LN)较NS组明显降低(均P＜0.05);各治疗组肝脏纤维化评分、Masson染色胶原沉积面积均较NS治疗对照组明显降低(均P＜0.01).结论 肝硬变大鼠接受门腔分流手术后,经门静脉输入肝营养因子(促肝细胞生长素+胰岛素)可以有效的改善大鼠的肝功能及肝细胞损害,并在一定程度上改善¨静脉高压大鼠的肝脏纤维化程度.     

血小板活性因子及其拮抗剂对大鼠肝硬化门脉高压的影响

目的探讨肝硬化时肝脏和血循环中血小板活性因子(PAF)的变化以及其对门脉高压的影响。方法CCl4腹腔注射8周(0·15ml/kg,2次/周)诱导大鼠肝硬化,快速3H-PAF液闪检测肝及循环中PAF水平;受体饱和结合实验分析肝组织PAF结合能力;监测外源性PAF及其拮抗剂BN52021对门脉压和系统动脉压的影响。结果与对照组相比,肝硬化时肝内PAF、肝脏输出PAF及肝内生PAF水平明显升高,分别4·0ng/g±0·4ng/gvs2·7ng/g±0·5ng/g(P<0·01)、6·3ng/ml±0·6ng/mlvs3·4ng/ml±0·6ng/ml(P<0·01)、1·0ng/ml±0·6ng/mlvs-0·3ng/ml±0·5ng/ml(P<0·01);肝组织PAF结合能力Bmax明显升高(2·8±0·21)fmol/μg膜蛋白vs(0·9±0·06)fmol/μg膜蛋白,P<0·01,而受体亲和力Kd差异无统计学意义(8·0nmol/L±1·3nmol/Lvs5·8nmol/L±1·0nmol/L,P>0·05)。肝硬化组基础门脉压升高(12·2mmHg±0·7mmHgvs5·3mmHg±0·6mmHg,P<0·01),系统动脉压降低(82mmHg±10mmHgvs114mmHg±9mmHg,P<0·01)。门脉注入PAF(1μg/kg)后,肝硬化组门脉压提高了32%(12·1mmHg±0·6mmHgvs16·0mmHg±0·7mmHg,P<0·01),升高幅度约为对照组的227%(4·1mmHg±1·0mmHgvs1·8mmHg±0·3mmHg,P<0·01),而系统动脉压在两组均下降(肝硬化组由82mmHg±10mmHg降至48mmHg±4mmHg,P<0·01;对照组由114mmHg±9mmHg降至52mmHg±4mmHg,P<0·01)。门脉注入BN52021(5mg/kg),肝硬化组门脉压降低了16%(14·6mmHg±1·6mmHgvs12·3mmHg±0·8mmHg,P<0·05),而系统动脉压在肝硬化组和对照组均无明显变化(P>0·05)。结论肝硬化时肝脏合成PAF明显增加是循环血PAF升高的重要来源,并上调节肝的血流动力学影响门脉高压形成,其作用可被其拮抗剂BN52021部分逆转。