17β-estradiol Attenuates Hypoxia-induced Pulmonary Vascular Remodeling via Downregulating miRNA-21 Signaling Pathway / 中国循环杂志

Objectives: To explore the effect of 17β-estradiol (E2) on hypoxic pulmonary hypertension (HPH) and explore if the effects were mediated through suppressing pulmonary artery smooth muscle cells (PASMCs) proliferation by targeting miRNA-21 (miR-21). Methods: Animal experiment: A total of 32 healthy female SD rats with castrated surgery were randomly divided into 4 groups: normoxia group, normoxia+E2 group, hypoxia group, hypoxia+E2 group (n=8 each). The rats in normoxia+E2 group and hypoxia+E2 group received subcutaneous injection of E2 20 μg/kg/d, and the rest groups received subcutaneous injection of equal volume saline. The hypoxic groups were placed in the hypoxic chamber (24 hours per day for 8 weeks) to establish HPH model and normoxic groups were kept in the room air. The pulmonary artery remodeling, mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI) were observed. Real-time PCR and Western blot were used to detect the levels of proliferation cell nuclear antibody (PCNA) and miR-21 expression in pulmonary artery. In vitro: human pulmonary artery smooth muscle cells (hPASMCs) were randomly divided into 3 groups: normoxia group, hypoxia group, hypoxia+E2 group. The levels of cell proliferation in each group were tested by MTT after 24 hours. Real-time PCR and Western blot were used to detect the levels of PCNA and miR-21 in cells. Results: Animal experiment: compared with normoxia group, the hypoxia group showed obviously thickened pulmonary artery wall, increased mPAP and RVHI, and significantly increased expression of miR-21 and PCNA (P<0.01);above changed were significantly attenuated in hypoxia+E2 group (P<0.01). In vitro: compared with normoxia group, the hypoxia group showed obvious proliferation and significantly increased expression of miR-21 and PCNA (P<0.01);compared with hypoxia group, the proliferation of hPASMCs and expression of miR-21 and PCNA were obviously reduced in hypoxia+E2 group (P<0.01). Conclusions: E2 could effectively reduce mPAP, attenuate the degree of right heart hypertrophy and pulmonary vascular remodeling, the protective effect may be mediated through downregulating miR-21 and PCNA expression, and subsequently inhibiting the proliferation of hPASMCs.

Inhibitory effects of celecoxib combined with capecitabine on H22 hepatoma mice and its mechanism / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the inhibitory effect and its mechanism of celecoxib combined with capecitabine on the growth of implanted H22 hepatoma in mice.</p><p><b>METHODS</b>Tumor model was established by hypodermical injection of H22 cells in BALB/c nude mice. Forty mice were equally randomly divided into 4 groups: control group, celecoxib group (receiving 100 mg/kg celecoxib), capecitabine group (receiving 755 mg/kg capecitabine), and combined treatment group (receiving 100 mg/kg of celecoxib and 755 mg/kg of capecitabine). From the third post-implantation day, each mouse was given relevant drug (or normal saline) by oral gavage. Fifteen days later, all mice were sacrificed and the tumor tissues were measured. The mRNA and protein levels of nuclear factor kappa-B (NF-ΚB) p65 and cyclooxygenase (COX)-2 in tumor tissues were detected by the quantitative polymerase chain reaction (qPCR)and Western blotting, respectively.</p><p><b>RESULTS</b>The tumor inhibition rate was 30.2% in celecoxib group and 49.9% in capecitabine group, which was significantly lower than that (75.4%) in the combined treatment group (P<0.01,P<0.05, respectively). qPCR showed a significant decrease of the mRNA expression of COX-2 in celecoxib group and combined treatment group when compared with control group (P<0.001), but no significant change in NF-ΚB p65.Capecitabine had no significant effects on the mRNA expression of COX-2 and NF-ΚB p65. Western blotting showed that celecoxib and combined treatment significantly inhibited the protein expression of COX-2 and NF-ΚB p65(P<0.05), but not capecitabine.</p><p><b>CONCLUSION</b>Celecoxib can enhance the antitumor effect of capecitabine by inhibiting the expressions of COX-2 and NF-ΚB p65 in mice bearing H22 implanted tumor.</p>

Alveolar cells apoptosis and Fas/FasL expression in rabbits after ischemia/reperfusion of pulmonary artery / 第二军医大学学报

Objective: To observe the changes of alveolar cells apoptosis and the expression of Fas/FasL protein in pulmonary injury induced by ischemia/ reperfusion in rabbbits, and to explore the related mechanism of pulmonary injury. Methods: The left pulmonary arteries of 30 healthy New Zealand rabbits (either sex) were obstructed and reperfused by inflating and discharging gas of 5F Berman sacculus catheter. The rabbits were then randomly divided into 5 groups: sham operation group, ischemia 1 h group, ischemia 2 h group,ischemia 2 h and reperfusion 1 h group,and ischemia 2 h and reperfusion 2 h group. Another 6 healthy rabbits were taken as control. The pulmonary tissues were harvested after experiment and the lung wet/dry ratio was determined. Alveolar cells apoptosis and Fas/FasL protein expression were determined using flow cytometry and immunocytochemistry techniques,respectively. Results: The lung cell apoptosis was obviously increased in ischemia groups compared with that in the control and sham group. The reperfusion after ischemia further increased the cell apoptosis compared with simple ischemia groups, and the apoptosis was positively related with the reperfusion time (P<0.05 or 0.01). Fas and FasL protein expression was significantly higher in ischemia and ischemia/reperfusion group than that in other groups (both P<0.01). Significant positive correlation was found between apoptosis index with lung wet/dry ratio and expression of Fas and FasL (r=0.769, 0.820,0.820 respectively, P<0.01). Conclusion: Pulmonary artery ischemia/reperfusion may activate the Fas/FasL system and induce alveolar cells apoptosis, leading to pulmonary damages.

Intervention effect of tongfei mixture on nocturnal hypoxia in patients with chronic obstructive pulmonary disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of tongfei mixture (TFM, a Chinese recipe mainly consisted of angelica and rehmannia root) on nocturnal hypoxia in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Sixty patients with COPD of remission phase were randomly divided into 3 groups, 20 in each group. Group A was the control group; Group B, the group simply treated with oxygen; Group C, treated with oxygen and TFM. Changes of pulmonary function, diaphragm muscle mobility (DMM), 6 min walk distance (6MWD), morning arterial blood gas, nocturnal lowest oxygen saturation (LSaO2), mean blood oxygen saturation (MSaO2), the percentage of saturation lower than 90% time account for total sleeping time (SLT90%) and ultrasonocardiogram before and after treatment were observed.</p><p><b>RESULTS</b>Levels of LSaO2, MSaO2 and SLT90% in Groups B and C were significantly higher than those in Group A (P<0.05, P<0.01). The lowering of PaCO2 in Group C was more significant than that in Group B (P<0.05). The mPAP level in Group C was lower, FEV1, 6MWD and DMM were improved than those in Group A and B, showing significant difference (P<0.05).</p><p><b>CONCLUSION</b>Combined use of oxygen therapy and TFM could not only improve the nocturnal hypoxia, but also lower PaCO2. TFM is an important supplement of oxygen therapy.</p>

Clinical observation on effect of auricular acupoint pressing in treating sleep apnea syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the clinical effect and mechanism of auricular acupoint pressing (AAP) in treating sleep apnea syndrome (SAS).</p><p><b>METHODS</b>Forty-five patients with SAS were randomly divided in to the AAP group (30 patients) and the control group (15 patients) to observe the changes of clinical symptoms, apnea-hypopnea index (AHI), apnea index (AI), hypopnea index (HI) and minimum blood oxygen saturation (mSaO2) in night before and after treatment by multiple channel polysomnography (PSG).</p><p><b>RESULTS</b>Clinical symptoms were significantly alleviated in the AAP group after treatment, with improvement in various parameters monitored by PSG (P < 0.01), showing significantly reduced AHI, AI and HI and increased mSaO2 (P < 0.01). While in the control group, no improvement was found either in clinical symptom or in PSG parameters (P > 0.05). Comparison between the two groups showed significant difference (P < 0.01).</p><p><b>CONCLUSION</b>AAP is an effective treatment of SAS, it provides a facilitate, economic and safe therapy for early prevention and treatment to SAS.</p>