1.The influence of ursolic acid on VEGF, COX-2 and MMP-2 expressed in the mouse retinal ischemic model
Ling HE ; Xiaolong ZHENG ; Xiao WANG ; Zhonghua WEN ; Jingjing GUO
Journal of Chinese Physician 2014;(4):443-446
Objective To investigate the influence of ursolic acid on vascular endothelial growth factor ( VEGF) , cycloxygen-ase-2 (COX-2), and matrix metalloproteinases-2 (MMP-2) expressed in the mouse retinal ischemic model , and to explore the mecha-nisms of anti-angiogenesis.Methods Sixty 7-day clean-class C57BL/6J mice were divided randomly into 6 groups [ n =10 mice (20 eyes) per group]:blank control, model control (PBS), positive control (triamcinolone), and ursolic acid (UA) intervention (low-dose, medium-dose, and high-dose).Mice in the blank control group were raised in air , and mice in other groups in(75%±2%)O2 high-oxygen environment for 5 consecutive days .Mice in the model control group and breastfeeding mice were put back in air environ-ment (21%O2 ) on the 12th day after the new-born mice to induce the generation of retinal neovascularization .When models were suc-cessful, the drug treatments were applied immediately to the corresponding groups , with injection of 3μl of sterile PBS in model control group, 3 μl of 1.5, 3.00 and 6.0 μg UA in UA intervention group, and 3 μl of triamcinolone (1 ml∶40 mg) in positive control group, respectively.All mice were killed after overdose anesthesia on the 17th day.Their eyeballs were made into samples and retinal tissue pathological sections with H-E dying method.The positive expressions of VEGF , COX-2, and MMP-2 were detected with immu-nohistochemical method .The fresh retinal tissue homogenate was prepared to detect the protein expressions of VEGF , COX-2, and MMP-2 in retinal tissue with western blot method ,and mRNA expressions of VEGF , COX-2, and MMP-2 were detected with real-time fluorescent quantitative polymerase chain reaction ( RT-PCR) .Results According to protein and mRNA expressions of VEGF , COX-2,and MMP-2 in retinal tissue among six groups , protein expressions of VEGF , COX-2, and MMP-2 in model group were significantly higher than those in blank group ( P <0.05 ) .Each protein expression in the high UA intervention group was significantly lower than that in the model group ( P <0.05 ) .Each protein expression in the high UA intervention group was not significantly different from that in the positive group ( P >0.05 ) .Each protein expression in the high UA intervention group was significantly lower than that in the low UA intervention group( P <0.05).Conclusions UA inhibited expressions of VEGF, COX-2, and MMP-2 in retinal ischemia model .UA also played an inhibitory role in the formation of neovascularization , and this role was positively correlated with UA dose .
2.Effects of Simvastatin on Oxidative Stress and Cell Apoptosis in Aged Mice with Myocardial Ischemia-re-perfusion
Xiaolong LIAO ; Shouhong WANG ; Zhonghua WANG ; Weixin GUO ; Jianyi WEN ; Tiehe QIN
China Pharmacy 2016;27(19):2626-2628,2629
OBJECTIVE:To study the effects of simvastatin on oxidative stress and cell apoptosis in aged mice with myocardi-al ischemia-reperfusion (IR). METHODS:Aged mice were randomly divided into sham operation group (phosphate buffer solu-tion),model group(phosphate buffer solution)and simvastatin low-dose,medium-dose and high-dose groups(2.5,5 and 20 mg/kg) with 14 mice in each group. Those groups were given relevant medicine intraperitoneally before modeling for 7 d,once a day. IR model was induced in those groups except for sham operation group. The area ratio of myocardial infarction,myocardial cell apop-tosis rate,activity of myocardial tissue apoptosis gene Caspase-3,the protein expression of Bax and Bcl-2,Akt phosphorylation, serum concent of MDA and activity of SOD were all detected. RESULTS:Compared with sham operation group,the area ratio of myocardial infarction,myocardial cell apoptosis rate,Caspase-3 activity,the protein expression of Bax and MDA content were all increased in model group,while the protein expression of Bcl-2,Akt phosphorylation and SOD activity were decreased(P<0.01). Compared with model group,the area ratio of myocardial infarction,myocardial apoptosis rate,Caspase-3 activity,the protein ex-pression of Bax and MDA content were all decreased in simvastatin high-dose group,while the protein expression of Bcl-2,Akt phosphorylation and SOD activity were increased (P<0.01). There was no statistical significance in above indexes in simvastatin low-dose and medium-dose groups (P>0.05). CONCLUSIONS:Simvastatin can relieve myocardial IR injury in aged mice,and the mechanism of which may be associated with inhibiting myocardial cell apoptosis and the generation of oxidative stress.
3.Effects of Chinese herbal medicine Huaiqihuang Granule on nephrin and podocin expressions in renal tissues of rats with adriamycin-induced nephrosis.
Wen SUN ; Zhi ZHU ; Jian YU ; Yonghong WANG ; Man XIONG ; Xia GAO ; Zhonghua ZHAO ; Xueguang LIU
Journal of Integrative Medicine 2011;9(5):546-552
Object: To investigate the effects of Huaiqihuang Granule, a compound Chinese herbal medicine, on expressions of nephrin and podocin of slit diaphragm of glomerular podocytes in rats with adriamycin-induced nephrosis and to explore the mechanism in reducing the proteinuria. Methods: Twenty SD rats were randomly divided into five groups: control group, model group, glucocorticoid group, Huaiqihuang Granule group and Huaiqihuang Granule plus glucocorticoid group. The 24-hour urine was collected 7, 14, 21 and 28 days after adriamycin injection respectively to measure 24-hour urinary protein, and all rats were sacrificed after 28-day treatment. Pathological changes in renal tissues were observed under a light microscope and an electron microscope. Expressions of nephrin and podocin mRNAs in renal cortex were determined by real-time polymerase chain reaction, and protein levels of nephrin and podocin were detected by Western blotting. Results: (1) In the model group and the treatment groups, the level of urinary protein increased significantly from the 14th day. (2) Under the light microscope, inflammatory cells and slight fibroplasia were found in renal interstitium of the model group, but there were less inflammatory cells in renal interstitium in the intervention groups than in the model group. Under the electron microscope, 29 days after adriamycin injection, extensive fusion of foot processes was observed. (3) The expressions of nephrin and podocin were higher in treatment groups than in the model group. (4) Proteinuria level was negatively correlated with the expressions of nephrin mRNA and nephrin and podocin proteins. Conclusion: The above results indicate that Huaiqihuang Granule can maintain the integrity of the slid diaphragram in podocyte, alleviate the lesion of glomerular filtration membrane, and decrease the proteinuria by up-regulating the expressions of nephrin and podocin. Huaiqihuang Granule plus glucocorticoid maybe has better effects than glucocorticoid alone.
4.Effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats
Zhonghua HU ; Rong HU ; Chengxuan QUAN ; Yi WANG ; Huijuan HE ; Guoxin LIN ; Kaiming DUAN ; Wen OUYANG
Chinese Journal of Anesthesiology 2011;31(11):1323-1326
ObjectiveTo investigate the effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats.MethodsTwenty-seven 22- month-old SD rats weighing 480-550 g were randomly divided into 2 groups: control group (group C,n =6) and isoflurane group (group Ⅰ,n =21 ).In group C inhaled mixed gas containing 80% oxygen for 2 h.In group Ⅰ the animals were endotracheal intubated after induction by 3% isoflurane and inhaled 2% isoflurane and 80% oxygen for 2 h.Cognition function was evaluated by Y-maze at 24 h after anesthesia and the total training times were recorded.The total training times > 75 was defined as cognitive dysfuction.In group Ⅰ the animals were divided into cognitive dysfuction group (group ⅠA) and non-cognitive dysfuction group (group IB) according to the results of Y-maze test.The animals were sacrificed and their hippocampi were removed and synaptosomes were extracted for two-dimensional gel electrophoresis.The different protein spots were analyzed by mass chromatographic analysis.ResultsSix rats had cognitive dysfuction (group IA) and another thirteen rats had no cognitive dysfuction (group IB).The total training times were significantly higher in group IA than in groups C and IB( P < 0.05).There was no significant difference in the total training times between groups C and IB (P > 0.05).There were 21 (11/10) different protein spots between groups IB and IA,and 19 (12/7) different protein spots between groups C and IA.Thirty-one protein spots were identified by means of MALDI-TOF-MS.ConclusionThe cognitive dysfuction after isoflurane anesthesia in aged rats may be related to the changes of energy metabolism protein,cytoskeletal structure and regulatory protein in synapse of hippocampus.
5.Effects of dexmedetomidine on postoperative cognitive function and monocytes Toll-like receptor 2 and Tolllike receptor 4 expression in elderly patients
Chengxuan QUAN ; Xiaoyu YANG ; Minghua CHEN ; Zhonghua HU ; Kaiming DUAN ; Qin LIAO ; Wen OUYANG
Chinese Journal of Anesthesiology 2011;31(11):1331-1334
ObjectiveTo investigate the effects of dexmedetomidine on postoperative cognitive function and monocytes Toll-like receptor 2 (TLR2)and TLR 4 expression in elderly patients.MethodsForty-five ASA Ⅰ or Ⅱ elderly patients aged ≥65 yr weighing 53-72 kg were randomly divided into 3 groups: control group (group Ⅰ ) and different doses of dexmedetomidine groups(groups Ⅱ and Ⅲ ).Dexmedetomidine 1.0 μg/kg was injected iv over 15 min after anesthesia induction,and then was infused at a rate of 0.5 μg·kg-1 ·h-1 (group Ⅱ ) or 1.0 μg· kg-1 ·h-1 (group Ⅲ ) untile the end of operation.Group Ⅰ received equal volume of normal saline.Blood samples were taken before anesthesia induction,at 1.5 h after the beginning of operation,at the end of operation and at 24 h after operation(T,-T5 ) for determination of monocytes TLR2 and TLR4 expression by flow cytometrybased method.Postoperative cognitive function was evaluated at 1 d before and 7 d after operation with Mini-mental state examination and Wechsler memory scale and Wechsler adult intelligence scale,and the postoperative cognitive dysfunction was recorded.ResultsThe incidence of postoperative cognitive dysfunction and monocytes TLR2 and TLR4 expression were significantly lower in groups Ⅱ and Ⅲ than in group Ⅰ,and in group Ⅲ than in group Ⅱ (P < 0.05).ConclusionDexmedetomidine can prevent postoperative cognitive dysfunction in elderly patients,and the mechanism may be related to down-regulation of monocytes TLR2 and TLR4 expression.
6.Biomechanical properties of compound ligament with small intestinal submucosa wrapping silk fibers
Shubei CUI ; Hong WANG ; Shuhua YANG ; Jingyuan DU ; Zengwu SHAO ; Chunqing MENG ; Deyu DUAN ; Changming WEN ; Xiaohong WANG ; Zhonghua LEI
Chinese Journal of Tissue Engineering Research 2007;0(03):-
0.05).CONCLUSION:The excellent mechanical properties of composite ligament can meet the mechanical requirements of appropriate ligament tissue engineering scaffolds.
7.Cryopreserved allogenic osteochondral pillars transplantation for cartilage defects
Changming WEN ; Hong WANG ; Shuhua YANG ; Chunqing MENG ; Deyu DUAN ; Haitao PAN ; Xin TANG ; Xiaohong WANG ; Shubei CUI ; Zhonghua LEI ; Qing FANG ; Liqun LI ; Chuan SUN
Chinese Journal of Tissue Engineering Research 2007;0(31):-
0.05), and the total score were similar in the two groups. Type Ⅱ collagen in the two groups was strongly positive by immunohistochemistry staining. CONCLUSION: Cryopreserved allogenic osteochondral pillars transplantation can repair small full-thickness articular cartilage defects. The chondrocytes are alive in short time, and they can secret cartilage matrix without obvious rejection. It has similar efficacy in histology with autogenic osteochondral pillar transplantation.
8.The correlation between hypoalbuminemia and prognosis in elderly patients after endovascular treatment
Ximing NIE ; Xiaoyu CUI ; Man LI ; Miao WEN ; Zhonghua YANG ; Liping LIU
Chinese Journal of Geriatrics 2020;39(11):1306-1310
Objective:To investigate the incidence of hypoalbuminemia in elderly patients undergoing endovascular treatment(EVT)for large vessel occlusion and to analyze the correlation between hypoalbuminemia and prognosis of EVT.Methods:A total of 640 elderly patients receiving EVT due to acute large vessel occlusion, aged(71.5±7.4)years with 377 males(58.9%), were enrolled into the prospective multicenter cohort study from July 2018 to May 2019.The patients were grouped as the low albumin group(serum albumin levels within 24 h after EVT <35 g/L, n=191, 29.8%)and as the normal albumin group(serum albumin levels≥35 g/L, n=449, 70.2%). The primary outcome was 90-day nerve functional independence defined by the modified Rankin Scale score 0-2.Outcomes were assessed as odds ratio( OR)by using multivariable logistic regression analysis. Results:The proportion of prognosis of good nerve functional independence at 90 d was lower in the low albumin group than in the normal albumin group[22.5%(43 cases) vs.41.9%(188 cases), OR=1.88, 95% CI: 1.20~2.95, P=0.01]. The incidence of early neurological deterioration was higher after treatment( OR=0.57, 95% CI: 0.37~0.88, P=0.01), and the proportions of multiple systemic complications were higher( P<0.01)in the low albumin group than in the normal albumin group. Conclusions:Hypoalbuminemia after EVT is correlated with the poor prognosis at 90 d in elderly patients.Elderly patients with hypoalbuminemia after EVT have higher incidences of multiple systemic complications.
9.A study on effect of traditional Chinese medicine Simo decoction on acute respiratory distress syndrome
Zhonghua WANG ; Shouhong WANG ; Weixin GUO ; Xiaolong LIAO ; Yan WU ; Jianyi WEN ; Daozheng HUANG ; Jun LIANG ; Jie LI ; Tiehe HANBIAO ; Qin LI
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(6):565-569
Objective To investigate the effect of Simo decoction oral liquid on inflammatory in acute respiratory distress syndrome (ARDS) mouse serum and the bronchoalveolar lavage fluid (BALF) and to explore the mechanism.Methods Fifty BALB/c mice were divided into normal control group, ARDS model group, small, moderate and large dose Simo decoction oral liquid-treated groups (simplified as Simo groups) according to random number table method (n=10, in each group). The ARDS model mice were replicated by lipopolysaccharide (LPS) tracheal instillation, and the mice in normal control group were given the same amount of normal saline. Immediately after the success of modeling, the mice were gavaged with 1, 2, 4 times the equivalent dose Simo decoction oral liquid of 7.56 mL·kg-1·d-1 in small, moderate or large dose Simo groups respectively, and there was no intervention in the normal control group or ARDS model group. All the mice were sacrificed at 24 hours after the respective drug amount or normal saline was given in various groups. The lung samples were taken for histologic evaluation, and BALF and serum samples were analyzed for the tumor necrosis factor-α(TNF-α), interleukin (IL-1β, IL-6), and in the mean time the level of serum superoxide dismutase (SOD) was detected.Results The pathological observation of lung tissue showed: there was no obvious inflammatory exudation in lung tissue of mice in normal control group; the inflammatory exudation in lung tissue of mice was increased significantly, the level of TNF-α (ng/L: 1759±303 vs. 104±27, 2506±674 vs. 507±46), IL-1β(ng/L: 209±16 vs. 114±11, 7325±826 vs. 3513±498) and IL-6 (ng/L: 144±38 vs. 47±7, 126±38 vs. 15±7) in serum and BALF were significantly increased, and the content of SOD (kU/L: 40.26±2.54 vs. 50.68±3.75) in serum was significantly decreased in ARDS model group (allP < 0.05), indicating that animal model of ARDS was set up successfully. Compared with ARDS model group, in small, moderate and large dose Simo groups, the inflammation exudation in lung tissue of mouse was reduced, the levels of TNF-α, IL-1βand IL-6 in serum and BALF were reduced, and the content of SOD in serum was increased [serum: TNF-α(ng/L) was 1642±276, 1126±154, 817±102 vs. 1759±303, IL-1β(ng/L)was 198±12, 170±11, 141±13 vs. 209±16, IL-6 (ng/L) was 127±22, 82±16, 41±15 vs. 144±38, SOD (kU/L) was 42.11±1.64, 48.09±1.23 vs. 40.26±2.54; BALF: TNF-α(ng/L) was 2479±446, 1632±330, 1067±223 vs. 2506±674, IL-1β(ng/L): 6939±725, 5398±625, 4401±210 vs. 7325±826, IL-6 (ng/L): 106±30, 68±13, 34±10 vs. 126±38, allP < 0.05], showing the Simo decoction inhibiting the lung inflammation and the above levels of indexes inserum and BALF was in a dose-dependent manner, and the changes in large dose Simo group was the most significant 45.18±1.15, .Conclusions Simo decoction oral liquid can inhibit the inflammatory response of ARDS, reduce the oxidative stress and decrease the lung injury of mice with ARDS.
10.Predictive value of central venous-to-arterial carbon dioxide difference on the prognosis of elderly patients with sepsis
Zhonghua WANG ; Shouhong WANG ; Xiaolong LIAO ; Weixin GUO ; Yan WU ; Shenglong CHEN ; Jun LIANG ; Daozheng HUANG ; Jie LI ; Jianyi WEN ; Hanbiao LI ; Tiehe QIN
Chinese Critical Care Medicine 2018;30(8):727-730
Objective To investigate the predictive value of central venous-to-arterial carbon dioxide difference (Pcv-aCO2) on the prognosis of elderly patients with sepsis.Methods 208 elderly patients who met the diagnostic criteria of the Sepsis-3 and with the age of more than 60 years old, and admitted to intensive care unit (ICU) of Guangdong General Hospital from January to December in 2017 were enrolled. According to the prognosis, the patients were divided into death group (n = 46) and survival group (n = 162). The Pcv-aCO2, central venous oxygen saturation (ScvO2), serum procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluationⅡ (APACHEⅡ) were collected for all patients. The differences of each index between the two groups were compared. The correlations between Pcv-aCO2 and ScvO2, PCT, CRP, SOFA, APACHEⅡscores were analyzed respectively with Pearson correlation. The prognostic value of Pcv-aCO2 in elderly patients with sepsis was assessed by receiver operating characteristic curve (ROC).Results Compared with survival group, the Pcv-aCO2, PCT, CRP, SOFA and APACHEⅡscores in death group were significantly increased [Pcv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.13±3.33 vs. 4.40±2.65, PCT (μg/L): 31.41±12.83 vs. 3.01±2.69, CRP (mg/L): 130.51± 42.23 vs. 104.46±50.12, SOFA: 12.01±2.25 vs. 9.05±2.06, APACHEⅡ: 29.52±5.03 vs. 20.01±3.21, allP < 0.05], and ScvO2 in death group was significantly decreased (0.571±0.136 vs. 0.685±0.106,P < 0.01). Correlation analysis showed that the Pcv-aCO2 was negatively correlated with ScvO2 (r = -0.762,P = 0.001) and was positively correlated with PCT, CRP, SOFA and APACHEⅡscores (r value was 0.737, 0.625, 0.738, 0.713, respectively, allP < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of Pcv-aCO2 prediction of death in patients with sepsis was 0.826, the cut-off was 6.62 mmHg, the sensitivity was 84.7%, the specificity was 77.5%, the positive likelihood ratio was 3.76, and the negative likelihood ratio was 0.19.Conclusion Pcv-aCO2 has a great value in evaluating the prognosis of elderly patients with sepsis and can accurately determine the prognosis of sepsis.