The regulation of retinoid X receptor-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury / 生理学报

The aim of this study was to investigate the regulatory role of retinoid X receptor (RXR)-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury (PIRI) and the underlying mechanism. Seventy-seven male Sprague-Dawley (SD) rats were randomly divided into 7 groups (n = 11): control group, sham group, sham+9-cis-retinoid acid (9-cRA, RXR agonist) group, sham+HX531 (RXR inhibitor) group, ischemia/reperfusion (I/R) group, I/R+9-cRA group, and I/R+HX531 group. The unilateral lung I/R model was established by obstruction of left lung hilus for 30 min and reperfusion for 180 min in vivo. The rats in I/R+9-cRA and I/R+HX531 groups were given intraperitoneal injection of 9-cRA and HX531 before thoracotomy. After reperfusion, the left lung tissue was taken to evaluate the lung tissue injury, and the oxidative stress-related indexes of the lung tissue were detected by the corresponding kits. The lung tissue morphology and the ultrastructure of the alveolar epithelial cells were observed by HE staining and transmission electron microscope, respectively. The protein expression of RXR in lung tissue was observed by immunofluorescence labeling method, and the expression level of nuclear factor E2-related factor (Nrf2) protein was detected by Western blot. The results showed that, compared with the sham group, the I/R group exhibited obviously injured lung tissue, decreased SOD activity, increased MDA content and MPO activity, and down-regulated expression level of Nrf2 protein. Compared with the I/R group, the I/R+9-cRA group showed alleviated lung tissue injury, increased activity of SOD, decreased MDA content and MPO activity, and up-regulated expression levels of RXR and Nrf2 protein. The above-mentioned improvement effects of 9-cRA were reversed by HX531 treatment. These results suggest that RXR activation can effectively protect the lung tissue against I/R injury, and the mechanism may involve the activation of Nrf2 signaling pathway, the enhancement of antioxidant level and the reduction of oxidative stress response.

Improvement of Al18F-PSMA-BCH preparation and its preliminary imaging study / 中华核医学与分子影像杂志

Objective@#To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al18F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation.@*Methods@#The mixture of PSMA-BCH, AlCl3, potassium biphthalate and no-carrier loaded 18F- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al18F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al18F-PSMA-BCH PET/CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for biodistribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer.@*Results@#The non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was (38.0±3.5)% with the radiochemical purity >99% and the specific activity of (16.4±4.4) MBq/nmol. Al18F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosimetry of (152.89±33.43) μGy/MBq, while bones showed lower uptake ((11.10±1.23) μGy/MBq) than most organs. The effective dose of whole body was (0.013 5 ±0.002 5) mSv/MBq. Multiple bone metastases were observed by Al18F-PSMA-BCH PET/CT imaging in a patient with recurrent prostate cancer.@*Conclusions@#Al18F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.

Improvement of Al18 F-PSMA-BCH preparation and its preliminary imaging study / 中华核医学与分子影像杂志

Objective To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al18 F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation. Methods The mixture of PSMA-BCH, AlCl3 , potassium biphthalate and no-carrier loaded 18F- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al18 F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al18 F-PSMA-BCH PET/ CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for bio-distribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer. Re-sults The non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was (38. 0±3.5)％ with the radiochem-ical purity >99％ and the specific activity of (16.4±4.4) MBq/ nmol. Al18 F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosim-etry of (152.89±33.43) μGy/ MBq, while bones showed lower uptake ((11.10±1.23) μGy/ MBq) than most or-gans. The effective dose of whole body was (0.0135 ±0.0025) mSv/ MBq. Multiple bone metastases were ob-served by Al18F-PSMA-BCH PET/ CT imaging in a patient with recurrent prostate cancer. Conclusions Al18 F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.

Effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion induced myocardial injury in mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice.@*METHODS@#Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot.@*RESULTS@#Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA.@*CONCLUSIONS@#The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.

Effect of dexmedetomidine on apoptosis and CHOP in hypoxia/reoxygenation injury A549 cell / 中国应用生理学杂志

OBJECTIVES@#To investigate the effects of dexmedetomidine (Dex) on injury of A549 cells induced by hypoxia/reoxygenation(H/R)and the influence of C/EBP homologous protein (CHOP) expression.@*METHODS@#Logarithmic growth phase A549 cells(it originated from alveolar type Ⅱ epithelial cell line) were randomly divided into 4 groups (=10):normoxic control group (N), Dex group (D), hypoxia/reoxygenation group (H), hypoxia/reoxygenation + Dex group(HD). At the beginning of modeling, 1 nmol/L Dex was puted into D and HD groups. N and D groups were cultured in the normoxic incubator for 30 h. H and HD group were incubated in the anoxic cultivation for 6 h, fo llowed by normoxic culture for 24 h. Then A549 cells were observed under the inverted microscope to observe the morphological changes. Cell activity was detected by cell counting Kit-8(CCK-8) and the apoptosis index(AI) was detected by in situ end labeling (TUNEL) method. The expression of CHOP、glucose-regulated protein of molecular weight 78 kDa (Grp78)、cysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOP、Grp78 mRNA were detected by Western blot and RT-PCR.@*RESULTS@#Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The absorbance value in H group decreased obviously (<0. 01). The AI value and expression of CHOP, Grp78, caspase-3 proteins and CHOP, Grp78 mRNA were significantly increased (<0.01). Compared with H group, the cell damage in HD group was decreased, the absorbance value increased (<0.01), the number of apoptosis cells decreased relatively (<0.01), the expression of CHOP, caspase-3 protein and CHOP mRNA decreased (<0. 01).@*CONCLUSIONS@#Dex has notable effects against H/R injury, which may be related to effective inhibition of apoptosis mediated by the CHOP's signal path.

The effect of Yiqi Wenyang Huoxue Huatan Fang on hypoxia-hypercarbia induced pulmonary hypertension and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of Yiqi Wenyang Huoxue Huatan Fang (YWHHF) on alleviating hypoxia-hypercarbia pulmonary hypertension by inhibiting endothelial-mesenchymal transition (EndoMT) BMP-7/Smads pathway.@*METHODS@#Fifty male healthy SD rats of clean grede, weighting (180~220) g, were randomly divided into 5 groups (=10):normoxia group (N), hypoxia-hypercarbia group (HH); YWHHF high dose group (YH), middle dose group (YM) and low dose group (YL). The rats in N group were kept in normal oxygen environment, the remaining four groups were intermittently exposed to hypoxia-hypercarbia environment (9%~11% O, 5%~6% CO) for 4 weeks, 6 days a week, 8 hours per day. The rats in YH, YM, YL groups were received YWHHF gavage in a dosageof 0.6, 0.3, 0.15g/kg respectively (3 ml/kg),the rats in N and HH groups were received equal volume of normal saline. After 4 weeks, the mean pulmonary arterial pressure(mPAP) was detected,the right ventricular free wall and left ventricle plus ventricular septum were isolated to determine the right ventricular hypertrophy index. Lung ultrastructural changes were surveyed under an electronic microscopy, the changes of pulmonary artery structure surveyed by immunofluorescence, the mRNA levels of alpha-smooth muscle actin (α-SMA)、platelet endothelial cell adhesion molecule-1 (CD31)、bone morphogenetic protein-7 (BMP-7)、drosophila mothers against decapentaplegic protein1/5/8 (Smad1/5/8) were detected by RT-PCR, and the protein levels of α-SMA、CD31、BMP-7、p-Smad1/5/8 and Smad1/5/8 were detected by Western blot.@*RESULTS@#Compared with N group, mPAP and the right ventricular hypertrophy index were increased,some significant injuries also were discovered under microscopic observation,the mRNA and protein expression of α-SMA was increased, and the mRNA expressions of CD31、BMP-7、Smad1/5/8 were decreased in the other four groups, the protein expressions of CD31、BMP-7、p-Smad1/5/8 were decreased(<0.05). Compared with HH group, the above changes in YH、YM、YL groups were all improved (<0.05).@*CONCLUSIONS@#YWHHF can inhibit EndoMT to alleviate pulmonary hypertension, and the mechanism may be related to the promotion of the expression of BMP-7/Smads pathway.

The role of endoplasmic reticulum stress in pulmonary hypertension in rat induced by chronic hypoxia and hypercapnia / 中国应用生理学杂志

OBJECTIVE@#To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension.@*METHODS@#Forty SD rats were random-ly divided into four groups:normoxic control group (N), hypoxia hypercapnia group (HH), ERS inhibitor 4-phenylbutyric acid group (4-PBA), endoplasmic reticulum stress (ERS) pathway agonist tunicamycin group (TM), ten rats in each group.The mean pulmona-ry artery pressure (mPAP), mean carotid artery pressure (mCAP) and right ventricular hypertrophy index of rats in each group were measured.Pulmonary artery smooth muscle cells were identified by immunofluorescence α-smooth muscle actin (α-SMA).Morphologi-cal changes of lung tissue and pulmonary artery were observed by electron microscope.The apoptotic index of pulmonary artery smooth muscle cells in each group was detected by TUNEL.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and cysteinyl aspartate specific proteinase-12 (caspase-12) mRNA and protein in each group.@*RESULTS@#①Compared with the N group, the mPAP, the ratio of right ventricle weight to left ventricle plus ventricular septum weight[RV/(LV+S)]and the ratio of pulmonary artery wall area to total tube area (WA/TA) were increased (<0.01), and the ratio of pulmonary artery luminal area to total tube area (LA/TA) were decreased (<0.01), pulmonary artery smooth muscle cell apoptosis index were decreased (<0.05 or <0.01) in HH group, 4-PBA group and TM group.ERS related protein and mRNA expressions were increased, the differences were statistically significant.②Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of 4-PBA group were decreased ( <0.01), LA/TA and pulmonary artery smooth muscle cell apoptosis index were increased (<0.01, <0.05).The expressions of ERS related protein and mRNA were all decreased (<0.05 or <0.01).③Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of TM group were increased (<0.05 or <0.01), pulmonary artery middle layer thickened, LA/TA and pulmonary artery smooth muscle cell apoptotic index were decreased (<0.01).ERS related protein and mRNA expressions were increased with statistical significance except GRP78 protein.@*CONCLUSIONS@#Pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia may be related to the excessive proliferation of pulmonary artery smooth muscle cells and too little apopto-sis;ERS related factors (JNK, caspase-12 and CHOP) are involved in the regulation of pulmonary hypertension induced by hypoxia hypercapnia.

Effects of Potassium Supplementation in Patients With Left Ventricular Dysfunction After Coronary Artery Bypass Grafting / 中国循环杂志

Objectives: To investigate the effects of potassium supplementation after coronary artery bypass grafting (CABG) in patients with reduced left ventricular ejection fraction (EF < 50%). Methods: Present study retrospectively analyzed data from 200 CABG patients with cardiopulmonary bypass from January 2015 to June 2017. Patients were divided as heart failure with high ideal potassium supplement group (low EF<50%, potassium supplement to 5.0 mmol/L, n=41); heart failure normal potassium supplement group (low EF<50%, potassium supplement to 4.5 mmol/L, n=46); and normal potassium supplement group (normal EF>50%, potassium supplement to 4.5 mmol/L, n=113). The differences on related parameters during intraoperative and postoperative period were compared among the 3 groups. The primary endpoint was the incidence of atrial and ventricular arrhythmias requiring the use of lidocaine and amiodarone hydrochloride. Results :Atrial and ventricular arrhythmias requiring lidocaine and amiodarone hydrochloride were found in 13 patients (31.7%) in the ideal hyperkalemia group, while 28 (62.2%) in the normal hyperkalemia group needed both drugs (P=0.005). The blood pressure of ideal high potassium supplementation group was significantly higher than that of normal potassium supplementation group ([135.87±11.32] mmHg vs [111.21±31.31] mmHg, P<0.001). In the ideal hyperkalemia group, the time in the ICU was shorter ([3.92±0.98]days vs [5.12±1.12]days, P<0.001) and the hospitalization time was shorter ([10.54±2.14] days vs [13.54±2.01]days, P<0.001). There was no significant difference between the two groups in postoperative 24-hour urine volume, oxygen partial pressure, postoperative 24-hour bleeding volume and postoperative complications (P>0.05). Conclusions:The ideal potassium target of 5.0 mmol/L for patients with LVEF<50% CABG can reduce the incidence of arrhythmias that require the intervention of lidocaine and amiodarone hydrochloride during the perioperative period and shorten the stay time in the ICU.

Role of EndoMT in HHPH based on TGF-β/Smads signaling pathway and regulated by Yiqi-Wenyang-Huoxue-Huatan formula / 中国病理生理杂志

AIM:To investigate the relationship between transforming growth factor-β(TGF-β)/Smads signa-ling pathway and pulmonary arterial endothelial-mesenchymal transition(EndoMT)in hypoxia-hypercapnia pulmonary hy-pertension(HHPH)process and the regulatory effect of Yiqi-Wenyang-Huoxue-Huatan formula(YWHHF).METHODS:Healthy male SD rats were randomly divided into 5 groups:normal control(N)group,hypoxia-hypercapnia(HH)group, high-dose YWHHF(YH)group,middle-dose YWHHF(YM)group and low-dose YWHHF(YL)group.The rats in N group was housed in normoxic environment,and the rats in the other 4 groups were housed in hypoxia-hypercapnia environ-ment(9%~11%O2and 5%~6%CO2)for 4 weeks,8 h/d,6 d/week.The excess water vapor was absorbed by anhy-drous CaCl2,and CO2was absorbed by sodium hydroxide.The rats in YWHHF groups were put into the oxygen chamber before the same volume of YWHHF at different concentrations were given(200 g/L for YH group,100 g/L for YM group and 50 g/L for YL group).The average pulmonary artery pressure and the average carotid artery pressure were measured during the operation.After operation,the right ventricular free wall and left ventricle plus interventricular septum were col -lected for determining the right ventricular hypertrophy index.Moreover,the morphological changes of the lung tissues were observed under light microscope.The mRNA and protein levels of α-smooth muscle actin(α-SMA),CD31,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were detected by RT-PCR and Western blot.RESULTS:Compared with N group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were increased, the levels of CD31 were decreased(P<0.05), and the lung tissue damage was observed in the other 4 groups.Compared with HH group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were decreased, while the mRNA and protein levels of CD31 were increased.Moreover,the lung tissue damage was reduced in YH,YM and YL groups.CON-CLUSION:TGF-β/Smads pathway may be involved in the process of EndoMT under hypoxia and hypercapnia condition, and YWHHF may reduce EndoMT by inhibiting the expression of TGF-β/Smads pathway-related molecules.

Effect of hydrogen molecule on apoptosis-related proteins and Nrf2 signa-ling pathway in glomerular mesangial cells cultured with high glucose / 中国病理生理杂志

AIM:To investigate the role of hydrogen molecule on apoptosis-related proteins in glomerular me-sangial cells cultured with high glucose and to explore its possible mechanism.METHODS:Mouse glomerular mesangial cells cultured in vitro were divided into 4 groups:normal control group(C group,5.5 mmol/L glucose),mannitol group(G group,5.5 mmol/L glucose+19.5 mmol/L mannitol),high glucose group(H group,25 mmol/L glucose),high glu-cose+hydrogen-rich water group(HH group,25 mmol/L glucose+hydrogen-rich water),and cultured for 48 h.The pro-tein levels of Bax,Bcl-2,cleaved caspase-3,nuclear factor E2-related factor-2(Nrf2),heme oxygenase-1(HO-1)and NAD(P)H:quinone oxidoreductase-1(NQO-1)were determined by Western blot ,and the mRNA expression of HO-1 and NQO-1 was determined by RT-PCR.The level of intracellular reactive oxygen species(ROS)was detected by dihydro-ethidium method,and the activity of superoxide dismutase(SOD)was measured by WST-8 assay.RESULTS:Compared with C group,the protein levels of Bax and cleaved caspase-3 were up-regulated,and Bcl-2 was down-regulated in H group(P <0.05).No significantly difference of the protein levels mentioned above between C and HH group was observed. Compared with H group,the protein levels of Bax and cleaved caspase-3 were down-regulated,and Bcl-2 was up-regulated in HH group(P <0.05).The level of intracellular ROS was higher and the activity of SOD was lower in H group than those in C group(P<0.05).However,there was no difference of the SOD activity between C group and HH group.The level of intracellular ROS decreased and the activity of SOD increased in HH group as compared with H group(P<0.05). Compared with C group,clearly reduced protein expression of Nrf2,HO-1 and NQO-1,and decreased mRNA expression of HO-1 and NQO-1 in H group were observed(P<0.05).Compared with H group,the protein levels of Nrf2,HO-1 and NQO-1 as well as the mRNA levels of HO-1 and NQO-1 were obviously increased in HH group(P<0.05 ).CONCLU-SION:Hydrogen molecule inhibits the expression of pro-apoptotic proteins and induces the expression of anti-apoptotic pro-teins in glomerular mesangial cells cultured with high glucose.The mechanism may be related to activation of Nrf 2 signaling pathway.

Current development and considerations about intraoperative neuromonitoring in thyroid surgery / 中华内分泌外科杂志

Since intraoperative neuromonitoring has been invented,and after persistent developing,it has become an adjunct to laryngeal nerve protection and stand as an important role in localization and recognizing,identification of nerve function and injury mechanisms.This technique has been widespread in China in recent years,but lack of standardized application and pitfalls of this intraoperative neuromonitoring itself have become a major issue.Only by proceeding systematic training,promoting standardized procedures,researches and developments,this technique can maximize its potential and benefit both physicians and patients.

Excessive endoplasmic reticulum stress mediates brain damage in hypoxia hypercapnia induced pulmonary hypertension rats / 生理学报

The purpose of the present study was to investigate the effect of excessive endoplasmic reticulum stress (ERS) on the brain damage in hypoxia hypercapnia induced pulmonary hypertension (HHPH) rats. Forty healthy SPF male SD rats were randomly divided into four groups (n = 10 for each): control group, hypoxia hypercapnia group, ERS pathway agonist tunicamycin (TM) group and ERS pathway inhibitor 4-phenylbutyric acid (4-PBA) group. The rats of control group lived in normal environment, while the rats of other three groups were raised for four weeks in the tank with 8.5%-11% Oand 5%-6% CO. TM (0.08 mg/kg, twice a week) and 4-PBA (80 mg/kg, daily) were respectively intraperitoneally injected into the rats of TM and 4-PBA groups, and the hypoxia hypercapnia group was given the same volume of normal saline. The mean pulmonary artery pressure and heart perfusion of the rats were determined and recorded after four-week raising. Then the brain tissue of the rats were quickly taken out for the brain water content measuring and morphological changes observing. The Caspase-3 activity and the apoptotic index of the brain cells were also determined. The protein and mRNA expressions of p-JNK, Caspase-12, CHOP and GRP78 in brain tissues were detected by Western blot and RT-PCR. The results showed that compared with the control group, the mean pulmonary artery pressure, brain water content and brain cells apoptotic index, Caspase-3 activity, the protein and mRNA levels of p-JNK, Caspase-12, CHOP and GRP78 were increased (P < 0.05), and the brain tissues of the rats were obviously damaged in the rats raised in the hypoxia hypercapnia environment; compared with hypoxia hypercapnia group, the mean pulmonary artery pressure, brain water content, brain apoptotic index and Caspase-3 activity, p-JNK, Caspase-12, CHOP, GRP78 protein and mRNA expressions in TM group were increased (P < 0.05), and the brain tissues of the rats were obviously damaged, while all above changes were relieved in 4-PBA group (P < 0.05). These results suggest that excessive ERS may participate in the brain injury induced by HHPH in rats and inhibition of excessive ERS can relieve the brain injury in the rats with HHPH.

Effects of dexmedetomidine on hypoxia/reoxygenation injury-induced cell apoptosis and caspase-12 expression in A549 cells / 生理学报

To investigate the effects of dexmedetomidine (DEX) on hypoxia/reoxygenation (H/R) injury-induced cell apoptosis and caspase-12 expression, A549 cells were randomly divided into 4 groups: control group, DEX group, H/R group and DEX+H/R group. Cells of control and DEX groups were cultured in the normoxic incubator for 30 h. Cells of H/R and DEX+ H/R groups were incubated in the anoxic cultivation for 6 h, followed by normoxic culture for 24 h, and DEX (1 nmol/L) was added into the culture medium in DEX and DEX+H/R groups. Morphological changes were observed under the inverted microscope. Cell viability was detected by CCK-8. The apoptosis index (AI) of A549 cells was detected by TUNEL method. The activity of caspase-3 enzyme in cells was detected by using caspase-3 kit. The expressions of GRP78, caspase-12 protein and mRNA were determined by Western blot and RT-PCR respectively. Compared with control group, the morphological changes of the cultured cells were observed: some of the cell fusion occurred and the shape of the cells was multilateral; the cell viability was decreased significantly (P < 0.01), the number of apoptotic cells and the AI value, caspase-3 activity, and the expressions of GRP78, caspase-12 protein/mRNA were significantly increased (P < 0.01) in H/R group. While the administration of DEX alleviated the H/R injury-induced cell damage, obviously increased the cell viability (P < 0.01), significantly decreased the increment of apoptotic cells and the AI value induced by H/R injury (P < 0.01), and also dramatically decreased the H/R injury-induced high level of caspase-3 activity (P < 0.01) as well as high expression of caspase-12 protein and mRNA (P < 0.01). Taken together, the results suggest that DEX can effectively protect A549 cells from the H/R injury, which may be mediated by down-regulating the expression of caspase-12 and inhibiting cell apoptosis.

Evaluating efficacy of pulmonary thromboendarterectomy in treatment of chronic thromboembolic pulmonary hypertension using pulmonary perfusion tomography / 中国医学影像技术

Objective To evaluate the efficacy of pulmonary thromboendarterectomy (PTE) in treatment of chronic thromboembolic pulmonary hypertension (CTEPH) using 99Tcm-macroaggregated albumin (99 Tcm-MAA) pulmonary perfusion tomography.Methods Sixteen patients with CTEPH underwent 99Tcm-MAA pulmonary perfusion tomography before and 6-12 months after PTE.The perfusion defects and improvement both in pulmonary lobe and segment were observed pre-and post-PTE.Percentage of perfusion defect scores (PPDs％) were calculated and the change of systolic pulmonary artery pressure (SPAP) measured by echocardiography was also recorded.Results The postoperative SPAP was significantly lower than that before surgery ([36.56±8.47] mmHg vs [90.52±14.55] mmHg,t=14.14,P＜0.001).Before PTE,perfusion abnormalities were identified in 86 (86/96,89.58％) pulmonary lobes of 16 patients.In all of the 86 abnormal lobes,21 (21/86,24.42％) became normal,and the remaining 65 (65/86,75.58％) were improved after PTE.Perfusion defects were confirmed in 230 (230/304,75.66％) pulmonary segments of 16 patients before surgery.In all of the 230 abnormal segments,73 (73/230,31.74％) became normal,74 (74/230,32.17％) were improved and 83 (83/230,36.09％) remained unchanged after PTE.The mean PPDs％ decreased from (56.79±14.54)％ pre PTE to (28.20±15.24)％ at 6 12 months after PTE.The PPDs％ was positively correlated with homochronous SPAP (r=0.68,P＜0.001).Conclusion PTE can significantly reduce SPAP and improve the pulmonary perfusion in CTEPH patients.Pulmonary perfusion imaging can evaluate the curative effect of PTE.

Role of TRPC6 in pulmonary artery smooth muscle cells proliferation and apoptosis under hypoxia and hypercapnia / 生理学报

The present study was to investigate the role of TRPC6 in pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis under hypoxia and hypercapnia. PASMCs were isolated from chloral hydrate-anesthetized male Sprague-Dawley (SD) rats. Cellular purity was assessed by immunofluorescence staining for smooth muscle α-actin under fluorescence microscopy. Passage 4-6 PASMCs were starved for 24 h in serum-free DMEM and divided into 5 groups randomly: normoxia, hypoxia and hypercapnia, DMSO, TRPC6 inhibitor SKF-96365 and TRPC6 activator OAG groups. The normoxic group was incubated under normoxia (5% CO, 21% O, 37 °C) for 24 h, and the others were incubated with corresponding drugs under hypoxic and hypercapnic (6% CO, 5% O, 37 °C) atmosphere for 24 h. TRPC6 mRNA was detected by reverse transcription-PCR. TRPC6 protein was detected by Western blotting. The proliferation of PASMCs was performed by CCK-8 kit. Apoptosis of the PASMCs was detected using TUNEL assay. The [Ca]in the PASMCs was measured using Fura 2-AM fluorescence. The results showed that the expressions of TRPC6 mRNA and protein, and [Ca]were upregulated under hypoxic and hypercapnic conditions. Hypoxia and hypercapnia promoted cellular proliferation and inhibited apoptosis in the PASMCs. OAG enhanced the above-mentioned effects of hypoxia and hypercapnia, whereas SKF-96365 reversed these effects. These results suggest that TRPC6 may play a role in PASMCs proliferation and apoptosis under hypoxia and hypercapnia by regulating [Ca].

Effect of panax notoginseng saponins injection on the p38MAPK pathway in lung tissue in a rat model of hypoxic pulmonary hypertension / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of panax notoginseng saponins (PNS) injection on pulmonary artery pressure and the expression of p38MAPK in lung tissue of rats subjected to chronic hypoxia.</p><p><b>METHODS</b>Thirty adult male Sprague Dawley rats were randomly divided into three groups (ten in each group): rats in control group were exposed to normoxic condition and the rats in hypoxia group and PNS group were subjected to 4-week hypoxia, and PNS injection (50 mg · kg(-1) · d(-1)) was administrated intraperitoneally at 30 min in the PNS group daily before the rats were kept in the hypoxic chamber, while rats in the other two groups received equal dose of normal saline instead. After chronic hypoxia, mean pulmonary artery pressure (mPAP) and mean carotid artery pressure (mCAP) were measured. The heart and lung tissues were harvested, and right ventricle (RV) and left ventricle plus ventricular septum (LV+S) were weighed to calculate the ratio of RV/(LV+S). The expression of p38MAPK mRNA was determined by reverse transcription-polymerase chain reaction, the quantity of phosphorylated p38MAPK (p-p38MAPK) in rat lung tissues and pulmonary arterioles was determined by Western blot and immunohistochemistry.</p><p><b>RESULTS</b>Compared with the control group, mPAP and the ratio of RV/(LV+S) in the hypoxia group were increased, the expression of p-p38MAPK in pulmonary arterioles and p38MAPK mRNA in the lung were higher (P<0.05). The changes of these parameters in the hypoxia group were significantly attenuated by PNS treatment (P<0.05).</p><p><b>CONCLUSION</b>PNS injection was shown to prevent hypoxic pulmonary hypertension at least partly by regulating p38MAPK pathway.</p>

Effect of ERK1/2 on rat pulmonary artery smooth muscle cells Kv1.5 channel in the process of hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effect of ERK1/2 MAPK pathway on the expression of Kv1.5 channel, a voltage-gated potassium ion channel, in rat pulmonary artery smooth muscle cells (PASMCs) and its mechanisms during the process of hypoxia.</p><p><b>METHODS</b>The PASMCs derived from SD rats were cultivated primarily. The third to sixth generation of PASMCs were divided into 5 groups randomly: (1) Normal group (N); (2) Hypoxic group (H); (3) Demethy sulfoxide(DMSO) group (HD); (4) U0126 group (HU): 10 micromol/L U0126; (5) Anisomycin group (HA): 10 micromol/L anisomycin. There were three dishes of cells in each group. The cells in normal group were cultured in normoxic incubator (5% CO2, 37 degrees C), the cells in other groups were added to 0.05% DMSO in the hypoxic incubator (5% CO2, 2% O2, 37 degrees C), all cells were cultured for 60 h. RT-PCR and Western blot were used to detected the espressions of Kv1.5 mRNA and protein in PASMCs.</p><p><b>RESULTS</b>Compared with N group, the expressions of Kv1.5 mRNA and protein in H, HD and HA groups were reduced significantly (P < 0.05); Compared with H group and HD groups, Kv1.5 mRNA and protein expressions in HU group were increased sharply (P < 0.05). Compared with the HU group, Kv1.5 mRNA and protein expressions in HA groups were significantly lower (P < 0.05).</p><p><b>CONCLUSION</b>Low oxygen reduced Kv1.5 mRNA and protein expressions, U0126 could resistant the Kv1.5 channel lower expression caused by hypoxia. Anisomycin had no significant effect on Kv1.5 channel expression under hypoxia, but the expression of Kv1.5 was still significantly lower than the normal oxygen group. These data suggest that hypoxia may cause hypoxic pulmonary hypertension by interfering ERK1/2 signaling pathway to inhibit Kv1.5</p>

Dynamic changes of IL-1β in rat myocardium during hypoxia/ reoxygenation transition / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the expression profile of interleuki-1β (IL-1β) in rat myocardium at different time points during hypoxia/reoxygenation(H/R)transition.</p><p><b>METHODS</b>The isolated Langendorff perfused rat heart model was established.Forty SD rats were randomly divided into sham group (A group) and hypoxia/reoxygenation group (H/R group). The H/R group rats were subdivided into H/R 0.5 h group(B group), H/R 1 h group(C group), H/R 2 h group(D group)according to reoxygenation time. The left ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax) were continuously recorded. The concentration of interleukin-1β(IL-lβ) and creatine kinase-MB (CK-MB) in myocardium was measured by ELISA. The mRNA expression of IL-lβ in myocardium was determined by RT-PCR. Microstructure of myocardium was observed under light microscopy.</p><p><b>RESULTS</b>The value of LVDP and ±dp/dtmax in hypoxia/reoxygenation group rat were significantly lower than that in sham group(P < 0.05). The expression of IL-lβ and CK-MB at protein level and the expression of IL-1β at mRNA level in hypoxia /reoxygenation group were higher than that in sham group(P < 0. 05). There were significant differences of the above parameters among H/R 0.5 h, 1 h, 2 h group(P <0.05). The concentration of IL-1β and CK-MB, the mRNA expression of IL-1β were higher in H/R 2 h group than that of other groups(P < 0.05).</p><p><b>CONCLUSION</b>The high expression of IL-Iβ in myocardium after myocardial hypoxia /reoxygenation in rats might lead to. ischemia/reperfusion injury.</p>

Experimental study in detection of myocardial ischemia with stress dual-phase 18F-FDG myocardial PET/CT / 中华核医学与分子影像杂志

Objective To explore the value of stress dual-phase (early and delayed phases)18 FFDG myocardial PET/CT in detection of myocardial ischemia.Methods Ten swine were prepared as ischemic models and underwent 3 imaging procedures:pre-model stress (8 swine),post-model rest (8 swine)and post-model stress dual-phase imaging (10 swine).To perform stress dual-phase imaging,the tested subjects were fasted for more than 12 h and underwent early-phase PET imaging at 50 min after the intravenous injection of 18F-FDG (5 MBq/kg) for 10 mins,and followed by a dobutamine stress test,and then delayed-phase PET imaging at 50 min after the stress test for another 10 mins.The post-model rest dual-phase imaging was performed in almost the same way except that there was no dobutamine-loading.18F-FDG uptake image was qualitatively analyzed and classified into 4 levels:1 =no uptake,2 =diffuse uptake,3 =focal uptake,4=focal on diffuse uptake.Level 1 or 2 was considered as normal.If the focal uptake (level 3 or 4)was found on anterior wall or septum,ischemia was diagnosed.x2 test was used to determine the difference of the rate of ischemic myocardium between the two phases.18F-FDG uptake ratio of the anterior wall to posterior wall (K) of the left ventricle was calculated (K1 for early phase and K2 for delayed phase).Wilcoxon rank sum test was applied to determine the difference between K1 and K2.Results CAG showed LAD stenosis ＞70％ in all swine.In pre-model stress dual-phase imaging,no ischemia was detected at two phases (8/8 for level 1 or 2,0 for level 3 or 4).There was no significant difference between K1 and K2(1.08±0.10,1.11 ±0.10; Z =-1.48,P＞0.05).In post-model rest dual-phase imaging,the rate of ischemic myocardium was not significantly different between early and delayed phases (1/8,3/8 ; x2 =0.50,P＞0.05).There was no significant difference between K1 and K2(1.47±0.28,1.28±0.40; Z=-2.02,P＞0.05).In post-model stress dual-phase imaging,the rate of ischemic myocardium between the two phases was statistically different (4/10,10/10;x2=4.17,P＜0.05),and the difference between K1 and K2 was also significant (1.55±0.32,1.86±0.39; Z=-2.49,P＜0.05).Conclusion Stress dual-phase 18F-FDG myocardial PET/CT might be useful for the diagnosis of ischemia.

Effect of Xuebijing Injection on TLR4-NF-κB-TNF-α pathway of rats' myocardial anoxia/reoxygenation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the role of Xuebijing Injection (XBJI) in inhibiting inflammatory factors associated with anoxia/reoxygenation myocardial inflammatory response of rats.</p><p><b>METHODS</b>Totally 36 healthy male Sprague-Dawley rats, 280 ± 30 g were randomly divided into six groups, i.e., the normal control group (N group), the balanced perfusion group (BP group),the model group (M group),the low dose XBJI group (XBJI(L) group), the middle dose XBJI group (XBJI(M) group),and the high dose XBJI group (XBJI(H) group), 6 in each group. The myocardial anoxia/reoxygenation rat model was established by Langendorff isolated heart perfusion. The concentration of TNF-α in the myocardial tissue was detected by ELISA. The expression of nuclear factor kappa B p65 (NF-κB p65) protein and Toll like receptor 4 (TLR4) protein were detected using Western blot. The expression of NF-κB p65 mRNA and TLR4 mRNA was detected by RT-PCR. Ultrastructural changes of anoxia-reoxygenation rats' heart muscle were observed under transmission electron microscope.</p><p><b>RESULTS</b>Compared with the M group,the TNF-α concentration, expression levels of NF-κB p65 protein and mRNA, TLR4 protein and mRNA decreased to various degrees in the XBJI(L) group, the XBJI(M) group, and the XBJI(H) group. The TNF-α expression level decreased most significantly in the XBJI(L), group (P < 0.01), while other indices decreased most obviously in the XBJI(M) group (P < 0.01, P < 0.05). Expression levels of NF-κB p65 and TLR4 protein were obviously lower in the XBJI(M) group than in the XBJI(L) group (P < 0.05). There was no statistical difference in other indices among the three XBJI groups (P > 0.05). Myocardial fibers were loose and broken with disappearance of transverse striation, and mitochondrial cristae was dissolved and severely damaged in the M group. The aforesaid condition was improved after treated by XBJI, with the most obvious effect obtained in the XBJI(M) group.</p><p><b>CONCLUSIONS</b>Different doses of XBJI could attenuate inflammatory reactions after myocardial anoxia/reoxygenation rats' heart muscle through inhibiting TLR4-NF-κB-TNF-α signal transduction pathway. The best effect could be obtained by 4 mL/100 mL XBJI.</p>