Diet Rich in Saturated Fat Decreases the Ratio of Thromboxane/prostacyclin in Healthy Men

Objective To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane 62 (TXB2) and 6-keto prostaglandin F la (PGF la) in 27 healthy free-living male subjects aged 30 to 55 years. Methods It was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks. Results Serum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF lα (P<0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2. Conclusions Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats

BACKGROUND： Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin（PGI2） in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.METHODS： Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride（CCl4） corn oil solution combined with intermittent drinking of 5% alcohol, and agematched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1α（6-keto-PGF1α, a stable metabolite of PGI2） was tested via enzyme immunoassays and the expression of cyclooxygenase（COX） in mesenteric arteries was detected by Western blotting.RESULTS： In parallel with the increase of plasma 6-ketoPGF1α, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3＇, 5＇-cyclic monophosphothioate（Rp-cAMPS） partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats.Indomethacin significantly decreased the plasma 6-keto-PGF1α.Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats,whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.CONCLUSION： Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributedto the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.

RELATION OF MALIGNANT TUMOR TO PROSTACYCLIN AND THROMBOXANE

The level of 6-keto-PGF1αand thromboxane B2(TXB2) in Plasma was determined with radioimmunoassay in 58 normal subjects and 92 Patients with various cancers(including lung,hepatic,gastric,esophageal and pancreatic carcinoma).The results showed that 6-keto-PGF1α.In plasma was 10.21±2.75 Pg/ml,and TXB2 146.03±37.31 Pg/ml in normal individuals,the ratio of 6-keto-PGF1α to TXB2 was 0.07;while in cancer Patients 6-keto-PGF1αwas 27.5±16.9 Pg/ml and TXB2 315.4±173.4 Pg/ml, the ratio of 6-keto-PGF1αto TXB2 was 0.08.The values of 6-keto-PGF1αand TXB2 in plasma of cancer patients were 2.69 folds and 2.16 folds higher than that of the two groups,respectively.The difference between the two groups was statistically significant(P<0.01).It indicates that the synthesis and release of PGI2 and TXA2 of cancer tissues increases greatly as compared to the normals.The study also revealed that the size of tumor,metastasis and histological classification had no obvious relation to PGs.

Effect of Intra-arachnoid Space Perfusion on Thromboxane A and Prostacycline in Experimental Spinal Cord Injury

In order to understand the relation between TXA2- PGI2 and secondary trauma and the effect of intra-arachnoid perfusion of dexamethasone and verapamil on alteration of TXA,-PGI, following spinal cord injury, TXB2 and 6-keto-PGFconcentration and pathological changes in injured site 1, 2, 4 and 6 h after injury were studied using a rabbit spinal cord injury model by Allen's weight drop method.

Ligustrizini promotes prostacyclin release from cultured human umbilical cord vein endothelial cells

The endothelial cells derived from human umbilical cord vein were treated with 200 μg/ml ligustrizini. The inhibrtory rate of platelet aggregation of the supernatant from the cultured endothelial cells treated with ligustrizini was 91% and that of superna

EFFECTS OF MODULATED LDLs ON THE RELEASE OF ENDOTHELIN-1 AND PROSTACYCLIN BY ENDOTHELIAL CELLS IN CULTURE

Objective To study the releases of endothelin-1 and prostacyclin by endothelial cells in culture and to elucidate how these releases were influenced by smoke-treated low density lipoprotein. Methods We exposed en- dothelial cell cultures to native or oxidized low density lipoproteins,low density lipoproteins treated by dimethylsul- foxide-soluble particles from cigarette smoke or dimethylsulfoxide alones. The release of endothelin-1 was assayed by bioassay and the release of prostacyclin was assayed by radioimmunoassay. Results Low density lipoproteins treated by smoke significantly increased the release or endothelin-1 (P<0.025) and decreased the release of prostacyclin (P< 0.02) by endothelial cells in culture, contrast to native or dimethylsulfoxide-treated lipoproteins. Conclusion The main part or vasoconstrictor activity in conditioned medium from bovine aortic EC is endothelin-1.

Neuroprotective Effect of a Prostacyclin Agonist (ONO-1301) with Thromboxane Synthase Inhibitory Activity in Rats Subjected to Cerebral Ischemia

ONO-1301 has been developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In the present study, we investigated the cerebroprotective effect of ONO-1301 on post-ischemic injury induced by cerebral ischemia in rats. ONO-1301 (1 and 10 mg/kg) was administrated orally at reperfusion and then twice a day for 42 days. The cell damage induced by cerebral ischemia in the hippocampal CA1 was evaluated using both Nissl staining and proliferating cell nuclear antigen (PCNA) staining on the 42 days after cerebral ischemia. Activated astrocytes were evaluated using immunofluorescence staining with GFAP on the 42 days after cerebral ischemia. Spatial learning was assessed using a Morris water maze (MWM) task on the 56 days (i.e. after a 14 days washout period). ONO-1301- treated rats (1 and 10 mg/kg) significantly improved cell death in the hippocampal CA1, the number of PCNA-positive cells and astrocyte activation. The spatial learning of ONO-1301-treated rats compared with vehicle- treated rats in the MWM task. These results suggest that repeated treatment with oral ONO-1301 could prevent or limit post-ischemic brain damage. In particular, treatment with ONO-1301 within 7 days after ischemia is most effective to improve ischemic damage.

Effects of prostacyclin derivatives combined with valsartan therapy on the blood biochemical indexes in patients with early hypertensive nephropathy

Objective:To explore the effects of prostacyclin derivatives combined with valsartan therapy on the blood biochemical indexes in patients with early hypertensive nephropathy.Methods: A total of 110 patients with hypertensive nephropathy who were treated in the hospital between December 2014 and March 2017 were divided into control group (n=55) and experimental group (n=55) by random number table method. Control group received valsartan therapy, and experimental group received prostacyclin derivatives combined with valsartan therapy, which lasted for 20 weeks. The differences in the contents of renal function indexes, urinary protein indexes and endothelial injury markers were compared between the two groups before and after treatment.Results: Before treatment, the differences in the contents of renal function indexes, urinary protein indexes and endothelial injury markers were not statistically significant between the two groups. After 20 weeks of treatment, renal function indexes SCr, BUN, UA and CysC levels in peripheral blood of experimental group were lower than those of control group;urinary protein indexes ALB,β2-MG andα1-MG contents were lower than those of control group;endothelial injury markers ET-1 and E-selectin contents in peripheral blood were lower than those of control group whereas NO and CGRP contents were higher than those of control group.Conclusion: Prostacyclin derivatives combined with valsartan therapy can effectively optimize the renal function, reduce the urinary protein and alleviate the vascular endothelial injury in patients with early hypertensive nephropathy and improve the overall therapeutic effect.

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy.Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure.METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by were divided into two groups to receive intraperitoneal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α(TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay.RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P＜0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S:438±102 vs841±145 counts/30 min, P＜0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vsN/S: 22±5 vs 10±1 pg/mL, P＜0.05)and lower plasma levels of 6-keto-PGF1α (P＜0.001), but not total bilirubin or creatinine (P＞0.05), as compared with rats treated with N/S.CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.

Interaction of endothelin-1 and prostacyclin during pathological process in patients with ischemic cerebral infarction

Objective To investigate the interaction and c linical significance of changes in p lasma endothelin-1(ET-1)and prostacyclin(PGI 2 )concentrations in patients with isc hemic cerebral infarction.Methods Plasma ET-1and 6-keto-PGF 1 α(resistant metabolite of PGI 2 )concentrations were measured in 37p atients(study group)with ischemic cerebral infarction a nd 34healthy volunteers(control group)by ra-dioimmunoassay.Results Plasma ET-1concentrations in patie nts of study group were markedly higher than that of control group(P <0.01)and 6-keto-PGF 1 αconcentrations in patients of study group were significantly lower than that of control subjects(P <0.01).Plasma ET-1concentrations in control subjects were positively correlated with 6-k eto-PGF 1 αconcentrations and no correlation i n the study group.Conclusion Both ET-1and PGI 2 are participated in patho-physiolo gic process of ischemic cerebral inf arction.ET-1is a virulence factor a nd may play a deleterious role in ischemic cerebral infarction,PGI 2 is a conservancy factor and endogenetic antagonist of ET-1.It may provid e useful therapy parameter to find out ectogenesis PGI 2 or analog for treating the patients with ischemic cerebral infarction wi th reason.

Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

Mechanism of overproduction of plasma prostacyclin in portal hypertensive rats

Abstract Objective To evaluate the role of increased portal pressure and portosystemic shunting in elevated level of prostacyclin (PGI 2) 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 PGF 1 α with radio immunoassay. 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 PGF 1α (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 PGI 2 in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Furthermore, the concentrations of plasma PGI 2 in PHPH and IHPH rats were also significantly higher than those in PCS rats. Moreover, a closed positive correlation existed between plasma PGI 2 and FPP (r=0.67, P<0.001). Conclusions The results of the present study suggest that the elevated PGI 2 in portal hypertension is mainly due to the overproduction of PGI 2 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 PGI 2 mediated the hyperhemodynamics in portal hypertension.

Effects of nitric oxide inhibitor on prostacyclin biosynthesis in portal hypertensive rats

Objective To evaluate the effects of nitric oxide inhibitor on prostacyclin (PGI 2) biosynthesis and the role of PGI 2 in hyperhemodynamics of portal hypertension. Methods Sprague Dawley rats were divided into four groups: intrahepatic portal hypertension (IHPH) by injection of CCl 4, prehepatic portal hypertension (PHPH) by stenosis of the portal vein, end to side portacaval shunt (PCS), and sham operated controls (SO). Animals of each group were subdivided into 2 groups: systemic administration of nitric oxide inhibitor L NMMA and vehicle. The radioactive microsphere method was used for hemodynamic study. The level of plasma PGI 2 (6 keto PGF 1α ) was measured by radioimmunoassay.Results The characteristics of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance, and splanchnic vascular resistance were observed in IHPH, PHPH and PCS rats. The magnitude of hyperhemodynamics was in the order of PCS>PHPH>IHPH rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L NMMA to the baseline values of hemodynamics in SO rats. The baseline concentrations of plasma 6 keto PGF 1α (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 6 Keto PGF 1α in PHPH,IHPH and PCS rats were significantly higher than those in SO rats. Moreover, the concentrations were significantly higher in PHPH and IHPH rats than in PCS rats (P<0.05). After administration of L NMMA, the concentrations of plasma 6 Keto PGF 1α (ng/ml) in PHPH, IHPH, PCS and SO rats were 7.69±2.98, 5.68 ±2.66, 5.50±0.79, 5.02±2.86, respectively. As compared to the baseline value, the concentrations of 6 keto PGF 1α rats were slightly increased in IHPH, PHPH rats (P>0.05), but significantly increased in PCS and SO rats (P<0.05).Conclusions In this study, the hyperdynamic circulatory state in portal hypertensive rats and portacaval shunt rats was completely reversed by L NNMA to normal, but the level of 6 keto PGF 1α was still elevated. The results indicate that PGI 2 is not involved in hyperhemodynamics of portal hypertension.

前列环素、神经肽Y与子痫前期关系及对胎盘早剥的预测价值研究

目的:探讨前列环素、神经肽Y与子痫前期的关系及对胎盘早剥的预测价值。方法:选择120例子痫前期孕妇作为观察组,另选同期的120例正常妊娠孕妇作为对照组。比较两组血清前列环素、神经肽Y水平,分析前列环素、神经肽Y在不同严重程度的子痫前期孕妇中差异性,使用受试者工作特征曲线(ROC)分析前列环素联合神经肽Y对胎盘早剥的预测价值。结果:观察组血清前列环素水平低于对照组,神经肽Y水平高于对照组,两组比较差异均有统计学意义(均P<0.05);重度子痫前期组血清前列环素水平低于轻度子痫前期组,神经肽Y水平高于轻度子痫前期组,两组比较差异均有统计学意义(均P<0.05);经Pearson相关性分析,子痫前期孕妇24 h尿蛋白定量、血液黏度、红细胞压积与前列环素呈负相关(均P<0.05),与神经肽Y呈正相关(均P<0.05),血红蛋白、血小板计数与前列环素呈正相关(均P<0.05),与神经肽Y呈负相关(均P<0.05);经ROC曲线分析,血清前列环素联合神经肽Y预测子痫前期孕妇发生胎盘早剥的AUC为0.914。结论:子痫前期孕妇血清前列环素表达下调,神经肽Y表达上调,可能参与病情进展,两者联合预测胎盘早剥的效能较好。

前列环素类药物治疗肺动脉高压的研究进展

肺动脉高压是肺高血压的一类,可危及生命。以肺动脉压力升高、肺血管阻力增加为主要特征,进而导致右心衰竭和死亡。前列环素信号通路是肺动脉高压重要的通路之一,除前列环素类似物和前列环素IP受体激动剂外,作用于血栓素A2的药物也正处于研究中。此外,还有更多新型治疗药物进入临床试验。本文通过对上述药物的简要介绍,以期为治疗肺动脉高压的治疗提供参考。

心脉隆注射液在慢性肺源性心脏病患者中的应用效果

目的:探析心脉隆注射液在慢性肺源性心脏病患者中的应用效果。方法:选取2019年6月-2022年2月在徐州市铜山区中医院住院治疗的52例慢性肺源性心脏病患者为研究对象,根据入院先后顺序分为对照组与观察组,各26例。对照组予以常规治疗,观察组在对照组基础上予以心脉隆注射液治疗,比较两组前列环素、血栓素A2、血清白细胞介素6(IL-6)、干扰素γ(IFN-γ)、动脉血氧分压(PaO_(2))和动脉二氧化碳分压(PaCO_(2))水平。结果:治疗前,两组前列环素和血栓素A2水平比较,差异无统计学意义(P>0.05);治疗后,观察组前列环素水平高于对照组,血栓素A2水平低于对照组,差异有统计学意义(P<0.001)。治疗前,两组IL-6、IFN-γ水平比较,差异无统计学意义(P>0.05);治疗后,观察组IL-6水平低于对照组,IFN-γ水平高于对照组,差异有统计学意义(P<0.001)。治疗前,两组PaO_(2)和PaCO_(2)水平比较,差异无统计学意义(P>0.05);治疗后,观察组PaO_(2)水平高于对照组,PaCO_(2)水平低于对照组,差异有统计学意义(P<0.001)。结论:对慢性肺源性心脏病患者采用心脉隆注射液治疗,可改善患者心功能和血管内皮功能,提高患者预后效果。

胰腺癌相关性成纤维细胞中前列腺环素合成酶对胰腺癌细胞作用研究

目的探究胰腺癌相关性成纤维细胞(CAFs)中的前列腺环素合成酶(PGIS/PTGIS)对胰腺癌细胞增殖、迁移和侵袭能力的影响及相关作用机制。方法利用GEPIA、Kaplan-Meier等数据库分析PGIS在胰腺癌及正常胰腺组织中的表达差异;通过q-PCR检测PGIS在CAFs及人胰腺星状细胞(HPSC)中的表达差异;通过CoCl_(2)化学诱导构建肿瘤微环境缺氧模型,检测胰腺癌及CAFs细胞的PGIS表达水平;利用siRNA转染、慢病毒感染的方式分别构建敲低和过表达PGIS的CAFs细胞,通过CCK-8增殖、Transwell迁移及侵袭等实验探究敲低和过表达PGIS的CAFs细胞对胰腺癌细胞增殖、迁移和侵袭能力的影响;通过小鼠胰腺原位成瘤探究过表达PGIS的CAFs细胞在体内对胰腺癌细胞增殖的影响;通过Western blot检测过表达PGIS的CAFs细胞对胰腺癌PI3K/Akt通路相关蛋白表达的影响。结果GEPIA、Kaplan-Meier数据库分析显示,与正常胰腺组织相比,PGIS在胰腺癌组织中高表达,并且与患者不良预后相关(P<0.05);与HPSC细胞相比,PGIS在CAFs细胞中显著高表达(P<0.05);胰腺癌及CAFs细胞在缺氧微环境中PGIS的表达水平明显上调(P<0.05);与对照组相比,敲低CAFs中的PGIS后,胰腺癌细胞的增殖速率明显减慢,细胞迁移和侵袭数量均明显减少(P<0.05);与对照组相比,过表达CAFs中的PGIS后,胰腺癌细胞的增殖速率明显加快,细胞迁移和侵袭数量均明显增多(P<0.05);与对照组相比,过表达PGIS的CAFs在体内可促进胰腺肿瘤的生长(P<0.05);与对照组相比,过表达CAFs中的PGIS后可明显上调VEGFA、p-Akt的蛋白表达水平(P<0.05),也可明显上调FGF-2、α-SMA及MMP-9的mRNA水平(P<0.05)。结论PGIS在胰腺癌组织中呈高表达,CAFs中的PGIS可能通过调节PI3K/Akt信号通路正向调控VEGFA的表达上调,促进胰腺癌细胞的增殖和侵袭,参与胰腺癌的发生、发展。

补益强心片对心力衰竭患者血清线粒体偶联因子6、内源性前列环素的影响分析

【目的】观察补益强心片对慢性心力衰竭(CHF)患者血清线粒体偶联因子6(CF6)、内源性前列环素(PGI2)的影响。【方法】采用回顾性研究方法,收集2019年10月至2021年10月在河北省衡水市人民医院就诊的102例CHF气虚血瘀兼水停证患者,根据治疗方法的不同将患者分为观察组和对照组,每组各51例。对照组给予西医常规治疗,观察组在对照组的基础上给予补益强心片治疗,疗程为4周并随访1年。观察2组患者治疗前后左室射血分数(LVEF)、6 min步行距离(6MWD)、血清CF6、PGI2及血清氨基末端B型钠尿肽前体(NT-proBNP)、心肌肌钙蛋白I(cTnI)水平的变化情况,并比较2组患者的临床疗效、不良反应发生率及1年内再入院率。【结果】(1)治疗4周后,观察组的总有效率为94.12%(48/51),对照组为70.59%(36/51),组间比较(χ^(2)检验),观察组的临床疗效明显优于对照组(P<0.01)。(2)治疗后,2组患者的LVEF、6MWD均较治疗前明显改善(P<0.05),且观察组对LVEF、6MWD的改善幅度均明显优于对照组(P<0.01)。(3)治疗后,2组患者血清CF6、NT-proBNP、cTnI水平均较治疗前降低(P<0.05),血清PGI2水平均较治疗前升高(P<0.05),且观察组对血清CF6、NTproBNP、cTnI水平的降低幅度及对血清PGI2水平的升高幅度均明显优于对照组(P<0.01)。(4)观察组的不良反应发生率为3.92%(2/51),对照组为7.84%(4/51),组间比较,差异无统计学意义(P>0.05)。(5)随访1年,观察组的1年内再入院率为1.96%(1/51),明显低于对照组的17.65%(9/51),组间比较,差异有统计学意义(P<0.05)。【结论】补益强心片治疗CHF气虚血瘀兼水停证患者疗效确切,可有效改善患者心功能,提高患者运动耐力,减轻心肌细胞受损程度,调节血清CF6、PGI2表达,降低再入院率,且不良反应相对较少,具有较高的安全性。

血清PGI2、Ang2对子痫前期孕妇胎盘早剥的预测价值

目的:探讨血清前列环素(PGI2)、血管生成素2(Ang2)对子痫前期孕妇胎盘早剥的预测价值。方法:选取2020年3月至2022年9月广东省水电医院收治的子痫前期孕妇96例作为疾病组,同期选取正常妊娠孕妇96例作为正常组。比较两组孕妇的血清PGI2、Ang2水平,分析PGI2、Ang2与子痫前期的关系,采用受试者工作特征(ROC)曲线分析血清PGI2、Ang2对胎盘早剥的预测价值。结果:疾病组的血清PGI2、Ang2水平均低于正常组(P<0.05)。疾病组中,重度子痫前期患者的血清PGI2、Ang2水平均低于轻度子痫前期患者(P<0.05)。Pearson相关性分析显示,血清PGI2、Ang2与子痫前期患者的24 h尿蛋白量(24hUAER)呈负相关(r=-0.772、-0.831,P均<0.05)。ROC曲线分析显示,在预测子痫前期孕妇胎盘早剥的敏感度、特异度、曲线下面积(AUC)及其95%CI中,PGI2<25.38 pg/mL时分别为75.00%、78.57%、0.762(0.712~0.835),Ang2<6.27 ng/mL时分别为83.33%、80.95%、0.816(0.767~0.869)。结论:血清PGI2、Ang2与子痫前期的发生发展有关,血清PGI2、Ang2的表达水平下降提示子痫前期孕妇胎盘早剥的发生风险增加,二者有望作为预测胎盘早剥的指标。