In order to investigate pre-and postoperative changes of prostagladin E2 (PGE2) and cellular immune function in patients with gastric cancer (GC), we measured T cell subsets, natural killer cell activity (NKCA) and PGE2 in peripheral blood (PB) of 31 GC patients and 30 controls with APAAP method, LDH release method and radioimmunoassay respectively. The results showed：① a significantly higher levels of PGE2, and a markedly lower levels of CD+4/CD+8 ratio in GC patients before surgery as compared with the controls. The PGE2 had a significant negtive coorelation with CD+4/CD+8 ratio and NKCA respectively.②PGE2 in PB of GC patients gradully declined to normal levels after surgery, moreover PGE2 in tumor tissue was markedly higher than that in normal tissue, implying that the tumor may be the major source of PGE2 in PB. Dynamic determination of PGE2 in PB would be great valuable in evaluation of cellular immune state, to evaluate the effect of surgery and prognosis of patients with gastric cancer.
【Abstract】 Objective Prostaglandin E2 (PGE2) production increases in human tendon fibroblasts after the tendon injuries and repetitive mechanical loading in vitro. To analyze the relations between PGE2 and tendinopathy by observing the changes of collagen content and proportion after the Achilles tendon of rabbits is repeatedly exposed to PGE2. Methods Twenty-four Japanese rabbits (aged 3-4 months, weighing 2.0-2.5 kg, and male or female) were equally randomized into 2 groups according to injection dose of PGE2: low dose group (50 ng) and high dose group (500 ng). Corresponding PGE2 (0.2 mL) was injected into the middle segment of the Achilles tendon of hindlimb, the same dose saline into the same site of the other side as controls once a week for 4 weeks or 8 weeks. The Achilles tendons were harvested at 4 and 8 weeks after injection. HE staining was used to observe the cell structure and matrix, and picric acid-sirius red staining to observe the distribution and types of collagen fibers, and transmission electron microscopy was used to measure the density of the unit area and diameter of collagen fibers. Results HE staining showed that collagen structural damage was observed in low dose and high dose groups. Picric acid-sirius red staining showed that the content of type I collagen significantly decreased while the content of type III collagen significantly increased in experimental side of 2 groups at 4 and 8 weeks after injection when compared with control sides (P lt; 0.05). The content of type I collagen was significantly lower and the content of type III collagen and ratio of type III to type I were significantly higher in high dose group than in low dose group (P lt; 0.05). Transmission electron microscopy showed that the collagen fibers density of unit area was significantly lower and the diameter was significantly smaller in high dose and low dose groups than in the controls (P lt; 0.05), and in high dose group than in low dose group (P lt; 0.05). Conclusion Repeat exposure of the Achilles tendon of rabbit to PGE2 can cause the decrease of type I collagen, the increase of type III collagen, the reverse ratio of type I to type III, reduced unit density of collagen fibers, and thinner collagen fibers diameter, which is related with tendinopathy.
Objective Series of compl icated molecule signal pathway are involved in the bone regeneration. To explore the possibil ity of nuclear factore kappa B (NF-κB) which is taken as the “key activation” during the fracture healing and provide the laboratory evidence for the gene therapy of nonunion or delayed union of fractures. Methods Thirtythree adult male Wistar rats (weighing 180-220 g) were selected and divided randomly into 4 groups: group A (the control group, n=3), the rigth lower segments of radius were injected with normal sal ine 0.3 mL for 7 days, once per day; group B (Bay 11-7082 injection group, n=6), the middle and distal radius were injected with normal sal ine containing 50 μmol/L NF- κB inhibitor Bay 11-7082 0.3 mL for 7 days, once per day; group C (fracture group, n=12), the right middle and distal radius were cut by a sharp scissors to form per fracture model; and group D (Bay 11-7082 treatment group, n=12), based on group C, 0.3 mL of 50 μmol/L Bay 11-7082 were injected into the fracture site for 7 days, once per day. The callus tissues were harvested at 3, 7, 14, and 28 days after fracture for Western blot analysis, alkal ine phosphatase (ALP) activity assessment, prostaglandins E2 (PGE2) production assay, and histological observation. Results The rats of all groups were survivaltill the experiment completion. At 3 and 7 days after injection, there was no significant difference in the ALP activity and PGE2 production between group B and group A (P gt; 0.05); but group C was significantly higher than group A (P lt; 0.01) and group D was significantly lower than group A (P lt; 0.01). The expressions of NF-κB p65, bone morphogenetic protein 7 (BMP-7), and inhibitor of DNA binding 2 (Id2) were observed at fracture sites of 4 groups. There was no significant difference in the expressions of NF-κB p65, BMP-7, and Id2 between group B and group A (P gt; 0.05); the expressions of NF-κB p65 and BMP-7 were significantly higher and the expression of Id2 was significantly lower in group C than group A (P lt; 0.01); and the expressions of NF-κB p65 and BMP-7 were significantly lower and the expression of Id2 was significantly higher in group D than group A (P lt; 0.01). The histological observation showed that a lot of osseous callus formed in group C at 14 and 28 days, but osseous callus just began to form in group D at 28 days. Conclusion NF-κB p65 can facil itate early fracture heal ing of rat radius by elevating the PGE2 production and regulating BMP-7 and Id2 expression.
目的：探讨在不同年龄SD大鼠右心房注射前列腺素E2（PGE2）对呼吸的影响。方法：7～9 d和21～23 d大鼠在迷走神经完整和迷走神经切断的情况下从右心房注射PGE-2，观察呼吸指标的变化。结果：①右心房注射PGE2在7～9 d和21～23 d大鼠中均引起呼吸暂停，呼气延长时间分别为基础呼气时间的9.5和7.5倍（Plt;0.05）；②切断迷走神经后，右心房注射PGE-2在7～9 d和21～23 d大鼠均不再产生呼吸暂停，仅出现轻微呼吸抑制。结论：右心房注射PGE2在7～9 d和21～23 d大鼠均产生呼吸暂停，且依赖于迷走神经的完整性。
Objective To explore the effects of dioscin (Dio) on airway inflammation and microRNA-155 (miR-155)/cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathways in asthmatic mice. Methods Seventy mice were randomly divided into control group, model group, inhibitor negative control group (inhibitor-NC group), miR-155 inhibitor group, and Dio group, Dio+miR-155 mimic negative control group (Dio+mimic-NC group), Dio+miR-155 mimic group, with 10 mice in each group. Using house dust mite to induce the preparation of asthma mouse models; enzyme linked immunosorbent assay was used to detect the levels of PGE2, tumor necrosis factor α (TNF-α), cysteyl leukotrienes (CysLTs), cysteyl leukotriene receptor 1 (CysLTR1) and interleukin (IL)-4, IL-5, IL-13 in mouse bronchoalveolar lavage fluid (BALF); hematoxylin-eosin and periodic acid-Schiff staining were used to observe the infiltration of inflammatory cells around the airway and the secretion of mucus by goblet cells; quantitative real-time PCR was used to detect the expression levels of miR-155 and COX-2 mRNA in mouse lung tissue; Western blot was used detect the expression of COX-2 protein in mouse lung tissue. Results MiR-155 inhibitor and Dio could reduce the levels of PGE2, TNF-α, CysLTs, CysLTR1 and IL-4, IL-5, IL-13 in BALF of asthmatic mice, reduce lung tissue inflammatory cell infiltration and goblet cell mucus secretion, and reduce lung tissue miR-155, COX-2 mRNA and protein expression; and miR-155 mimic could significantly weaken the anti-asthma effect of Dio. Conclusion The anti-asthma effect of Dio may be related to the inhibition of miR-155/COX-2/PGE2 pathway to reduce airway inflammation in asthmatic mice.
Objective To explore the role and possible mechanisms of bone marrow mesenchymal stem cell (BMSC) in the lipopolysaccharide (LPS)-induced inflammatory response involving alveolar macrophages through the inflammatory pathways. Methods ptges and ptges shRNA were transfected into BMSC by lentivirus, and stable ptges overexpression BMSC (BMSC-PGE2(+)) and PTGEs silencing BMSC (BMSC-PGE2(-)) were established. Macrophages were divided into control group, LPS group, LPS+BMSC group, LPS+BMSC-PGE2(+) group and LPS+BMSC-PGE2(-) group. The expression levels of nucleotide-bound oligomerized domain-like receptor 3 (NLRP3), precursor cysteinyl aspartate specific proteinase 1 (pro-caspase-1), caspase-1 and pro-IL-1β proteins were detected by Western blot. The mRNA expression levels of NLRP3 and caspase-1 were determined by RT-PCR. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, IL-18 and prostaglandin E2 (PGE2) in cell supernatant were detected by ELISA. Results The intervention of LPS significantly increased the expression of NLRP3, pro-caspase-1, caspase-1 and pro-IL-1β in macrophages. After co-culture with BMSC, the expression of each protein decreased significantly. After the overexpression of PGE2, the difference of protein expression further decreased. The expression of NLRP3 and caspase-1 mRNA in LPS group increased significantly, but decreased significantly after co-culture with BMSC. Overexpression of PGE2 could increase this difference, but there was no significant change in PGE2 silent group. The results of ELISA showed that the contents of TNF-α, IL-1β and IL-18 in cell supernatant were the highest in LPS group. Adding BMSC and overexpressing PGE2 could decrease the related inflammatory factors. The levels of IL-10 and PGE2 in LPS group were higher than those in control group, and further increased in LPS+BMSC group and LPS+BMSC-PGE2(+) group with significant differences. Conclusions When inflammation is induced by LPS, BMSC can significantly mitigate the inflammatory response within macrophages. This process is likely mediated through the overexpression of PGE2, which inhibits the NLRP3-mediated pyroptosis pathway.