1.Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats.
Ling-Heng KONG ; Xiao-Ming GU ; Xing-Li SU ; Na SUN ; Ming WEI ; Juan-Xia ZHU ; Pan CHANG ; Jing-Jun ZHOU
Journal of Southern Medical University 2016;36(5):633-638
OBJECTIVETo investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms.
METHODSThirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c.
RESULTSCompared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01).
CONCLUSIONBDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.
Animals ; Apoptosis ; Calcium ; adverse effects ; Caspase 3 ; metabolism ; Cytochromes c ; metabolism ; Diacetyl ; analogs & derivatives ; pharmacology ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; L-Lactate Dehydrogenase ; metabolism ; Male ; Myocardial Reperfusion Injury ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left
2.Inhibition of CaMKII alleviates myocardial ischemia?reperfusion injury by reducing mitochondrial oxidative stress in isolated perfused rat heart.
Ling-Heng KONG ; Yu-Long CHEN ; Na SUN ; Ming WEI ; Juan-Xia ZHU ; Xing-Li SU
Journal of Southern Medical University 2018;38(2):181-186
OBJECTIVETo investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms.
METHODSAn ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5 µmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox--CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA.
RESULTSCompared with the control group, KN-93 treatment at 2.5 µmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5 µmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01).
CONCLUSIONCaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.
3.Rat alveolar type II injured by bleomycin.
Lu KONG ; Zhi-gang WANG ; Jian-zhao NIU ; Ji-feng WANG ; Huan JIN ; Mei-juan YANG ; Ling-qiao WANG ; Bing-hua TANG ; Qiu-ju ZHANG ; Heng-jing TU
Acta Academiae Medicinae Sinicae 2005;27(1):81-86
OBJECTIVETo explore dysfunction mechanism of rat alveolar type II (AT-II) injured by bleomycin (BLM).
METHODSSD rats were injected with a single intratracheal dose of bleomycin or control saline. On day 7, 14, and 28 following intratracheal bleomycin or saline instillation, animals were killed under overdose of 1.5% sodium pentobarbital (0.25 ml/100 g, i.p.) and bronchoalveolar lavage fluid (BALF) from the lung was tested for the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance. Several concentrations of bleomycin stimulated the culture of rat AT-II cells, and surfactant protein (SP) A, B, and aquaporin-1 (AQP) mRNA were analyzed by fluorescent quantitative polymerase chain reaction (FQ-PCR).
RESULTSThe activity of PS and hypoxemia significantly decreased on day 7 and improved on day 14 and completely recovered to normal status on day 28. SP-A, B, and AQP-1 mRNA expression in BLM-stimulated group were significantly lower than those in the control group (P<0.001).
CONCLUSIONBLM-injured AT-II cells decrease the levels of SP-A, B, and AQP-1 mRNA and cause PS dysfunction, resulting in hypoxemia and pneumonedema.
Animals ; Aquaporin 1 ; biosynthesis ; genetics ; Bleomycin ; administration & dosage ; toxicity ; Cells, Cultured ; Dose-Response Relationship, Drug ; Epithelial Cells ; drug effects ; metabolism ; Hypoxia ; chemically induced ; metabolism ; pathology ; Male ; Pulmonary Alveoli ; cytology ; drug effects ; Pulmonary Surfactant-Associated Protein A ; biosynthesis ; genetics ; Pulmonary Surfactant-Associated Protein B ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Time Factors
4.Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging and comparison with single-photon emission computed tomography.
Yi-Ning WANG ; Zheng-Yu JIN ; Zhu-Hua ZHANG ; Ling-Yan KONG ; Li-Bo CHEN ; Lu ZHOU ; Hong-Yi SUN ; Heng ZHANG ; Qi MIAO
Chinese Medical Sciences Journal 2006;21(4):239-244
OBJECTIVETo compare contrast-enhanced magnetic resonance imaging (ceMRI) with nuclear metabolic imaging for the assessment of myocardial viability in patients with chronic ischemic heart disease.
METHODSTwenty patients with suspected chronic ischemic heart disease underwent ceMRI and technetium-99m sestamibi single-photon emission computed tomography (SPECT). Patients with positive SPECT results also underwent 18F-fluorodeoxyglucose (FDG) SPECT. In a 17-segment model, the segmental extent of hyperenhancement (SEH) by ceMRI was compared with segmental FDG and sestamibi uptake by SPECT. Correlation between the extent of hyperenhancement by ceMRI and left ventricular function was analyzed.
RESULTSSeven patients got negative results both in ceMRI and technetium-99m sestamibi SPECT. The rest 13 patients with positive results then underwent 18F-FDG SPECT. In 221 segments of 13 patients, SEH was (2.1 +/- 8.2)%, (25.0 +/- 13.7)%, and (57.7 +/- 23.6)% in segments with normal metabolism/perfusion, metabolism/perfusion mismatch, and matched defects, respectively, and there were significant differences between either two of them (all P < 0.05). By receiver operating characteristic curve analysis, the area under the curve was 0.95 for the differentiation between viable and non-viable segments. At the cutoff value of 34%, SEH optimally differentiated viable from non-viable segments defined by SPECT. Using this threshold, the sensitivity and specificity of ceMRI to detect non-viable myocardium as defined by SPECT were 92% and 93%, respectively. Hyperenhancement size by ceMRI was correlated negatively with the left ventricular ejection fraction (r = - 0.90, P < 0.01) and positively with left ventricular volumes (r = 0.62 for end-diastolic volume, r = 0.75 for end-systolic volume, both P < 0.05).
CONCLUSIONCeMRI allows assessment of myocardial viability with a high accuracy in patients with chronic ischemic heart disease.
Female ; Fluorodeoxyglucose F18 ; Heart ; diagnostic imaging ; Humans ; Image Enhancement ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Myocardial Ischemia ; diagnosis ; diagnostic imaging ; physiopathology ; Myocardium ; pathology ; Sensitivity and Specificity ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; methods
5.Surgical treatment for 140 patients with gastric stromal tumors.
Xiao-jun WU ; Yu-jin FANG ; Zhen-hai LU ; Jun-zhong LIN ; De-sen WAN ; Pei-rong DING ; Gong CHEN ; Li-ren LI ; Ling-heng KONG ; Zhi-zhong PAN
Chinese Journal of Gastrointestinal Surgery 2010;13(6):417-420
OBJECTIVETo analyze the outcome of the patients with gastric gastrointestinal stromal tumor(GIST) after surgical treatment and identify the associated risk factors.
METHODSClinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis.
RESULTSThe overall survival rates of 1-, 3-, 5-year were 96.8%, 86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P<0.05). Gender, preoperative metastasis, tumor size,pathology type,karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis(P<0.05).
CONCLUSIONSurgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.
Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Stromal Tumors ; surgery ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Survival Rate ; Treatment Outcome ; Young Adult
6.Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers.
Fu-long WANG ; De-sen WAN ; Zhen-hai LU ; Yu-jing FANG ; Li-ren LI ; Gong CHEN ; Xiao-jun WU ; Pei-rong DING ; Ling-heng KONG ; Jun-zhong LIN ; Zhi-zhong PAN
Chinese Journal of Oncology 2013;35(4):277-281
OBJECTIVETo study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.
METHODSTwo hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.
RESULTSThe positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.
CONCLUSIONSVEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.
Aged ; Biomarkers, Tumor ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Microsatellite Instability ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Rectal Neoplasms ; metabolism ; pathology ; Retrospective Studies ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; metabolism
7.Surgical treatment for gastrointestinal stromal tumor.
De-Sen WAN ; Xiao-Jun WU ; Pei-Rong DING ; Zhi-Zhong PAN ; Zhi-Wei ZHOU ; Gong CHEN ; Li-Ren LI ; Zhen-Hai LU ; Ling-Heng KONG ; Xiao-Man LIANG ; Rong-Zhen LUO
Chinese Journal of Surgery 2007;45(15):1037-1040
OBJECTIVETo analyze the effects of surgical treatment for gastrointestinal stromal tumors (GISTs) and influential factors of survival.
METHODSThe clinical data and the tissue slices including immunohistochemical staining of 153 cases of GISTs from January 1990 to March 2006 were rechecked retrospectively. All patients were followed up carefully. More attention was paid to the surgical effects and the influential factors of survival.
RESULTSThe overall survival rates at 1-, 2-, 3-, 4- and 5-year were 94.9%, 83.3%, 73.3%, 70.5% and 64.3%, respectively. The median survival time for patients with tumor resected completely was 66.0 months, and the 2- and 5-year survival rate were 89.4% and 70.9% respectively. The median survival time was 23.8 months for the patients with tumor resected partly, and only two of these patients survived over 2 years. Gender, tumor sites, preoperative metastasis, tumor size, pathological type, karyokinesis and recurrence and metastasis were related with survival rates for the patients with tumor resected completely on univariate analysis, but tumor size, pathology type, recurrence and metastasis were related with survival rates on Cox regression multivariate analysis (P < 0.05).
CONCLUSIONSSurgery should still be the main therapy for GISTs. Local complete resection is the principal treatment. The survival cannot be improved by extensive resection and lymph nodes clearance.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; analysis ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; metabolism ; mortality ; surgery ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Proto-Oncogene Proteins c-kit ; analysis ; Retrospective Studies ; Survival Rate ; Treatment Outcome
8. Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice
Si-Yuan PAN ; Xue-Lan SONG ; Zhao-Heng LIN ; Hai-Chuan TAI ; Si-Yuan PAN ; Qing YU ; Yi ZHANG ; Gan LUO ; Xiao-Yan WANG ; Nan SUN ; Zhu-Sheng CHU ; Yi ZHANG ; Pei-Li ZHU ; Zhi-Ling YU ; Kam-Ming KO
Asian Pacific Journal of Tropical Biomedicine 2022;12(2):59-68
Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).