1.Establishment of two cardiac-specific human cardiac troponin C mutation transgenic mice and comparative analysis
Shan GAO ; Wei CHEN ; Ning LIU ; Wenping GE ; Xiang GAO ; Dan LU ; Lianfeng ZHANG ; Wei DONG
Chinese Journal of Comparative Medicine 2014;(3):67-71
Objective To established cardiac-specific transgenic mice of the cTnC D145E and cTnCG159D and compare the HCM and the DCM.Methods The cTnCD145E and cTnCG159D were generated by site-directed mutagenesis and the transgenic plasmids were constructed by insertion of the mutant genes under the control of α-MHC, which is a myocardium specific promoter.The transgenic mice were generated by microinjection and were all maintained on a C57BL/6J genetic backgroud .The cardiac structure and function of the transgenic mice were compared and analysized by echocardiographic and pathological observation at different ages .Results The cTnCD145E and cTnCG159D transgenic mice were established and developed to HCM and DCM, respectively, with aging.The left ventricular end-systolic volume (ESV) and left ventricular end-diastolic volume ( EDV) decreased and ejection fraction ( EF) and left ventricular end-systolic posterior wall thickness (ESPWT) increased in the cTnCD145E transgenic mice, while EDV and ESV increased and EF and ESPWT decreased in the cTnCG159D transgenic mice at 12 months of age.Conclusions Cardiac-specific human cTnCD145E transgenic mice showed HCM phenotypes , and cardiac-specific human cTnC G159D transgenic mice showed DCM phenotypes , which can be used as different models for comparative study of the pathogenesis of cardiomyopathy .
2.Establishment of the psoriasis transgenic mouse model and analysis of the phenotype
Xiang GAO ; Ning LIU ; Wenping GE ; Shuo PAN ; Haitao ZHANG ; Lianfeng ZHANG ; Wei DONG
Chinese Journal of Comparative Medicine 2015;(7):11-15
Objective To develop a model that could copy the pathological development of psoriasis, the triple-transgenic mice that harboring Plasminogen activator, urokinase ( PLAU) ,PLAU receptor ( PLAUR) and signal transducer and activator of transcription 3 ( STAT3 ) were generated.They are the important genes involved in the pathological development of psoriasis.Methods The transgenic plasmid was constructed by insertion of the PLAU, PLAUR and STAT3 into the downstream bovine keratin 5 promoter respectively.The transgenic mouse was produced by microinjection and the genotyping was detected by PCR.The expression level of the transgenic gene was determined by Western blotting.The pathological changes were observed by HE staining.Results One mouse line was selected with over expression of the PLAU, PLAUR and STAT3 in the tissue of skin.The transgenic mice showed decreased dermal layer, a hyperkeratinized cuticular layer and increased stratum spinosum.The number of hair follicle was reduced and developed abnormally in the transgenic mice.The Munro abscess in the dermal layer and the increased inflammatory cell infiltrates in dermal layer were also observed in the transgenic mice.Conclusions A transgenic mouse line was produced and passage stably, which expressed the PLAU, PLAUR and STAT3 in the tissue of skin and developed the psoriasis progressively.All of our results suggested that the transgenic mice were a useful animal model for psoriasis.
3.The intervention effects of sodium aescinate on acute lung injury model of rats induced by oleate
Wei TIAN ; Wenping SUN ; Xiaohui DENG ; Qiang XUE ; Tianshui LI ; Zhifang CHEN ; Hongfang JIN ; Bin ZHAO ; Junbao DU ; Baoming GE
Chinese Pharmacological Bulletin 2009;25(12):1589-1594
Aim To observe the intervention effects of sodium aescinate on acute lung injury model of rats induced by oleate. Methods Fifty four male SD rats were randomly divided into five groups: normal control group, sodium aescinate control group (without oleate) , oleate model control group,medrol interventional group and sodium aescinate interventional group. Acute lung injury models of rats were made by injecting oleate (OA, 0. 1 ml · kg~(-1) ) through caudal veins, and then rats were observed and killed to detect correlated in-dice. The observation indice were the histomorphology of lung, the wet and dry weights of lung ( W/D), score of injury of lung under light microscope (IQA ) , partial pressure of oxygen in artery ( PaO_2) , the levels of SOD and MDA in blood plasma and lung tissue. Results ① Histomorphology of lung: Lung surface hyperemia relieved obviously and pink secretion from trachea of rats in sodium aescinate interventional group and medrol interventioal group decreased significantly compared with oleate model control group. Under light microscope , compared with oleate model control group, effusion of inflammatory cells in alveolar space of rats in sodium aescinate interventional group and medrol interventional group decreased. ② The wet and dry weights of lung ( W/D ) ; W/D of rats in oleate control model group increased obviously compared with those in normal control group, W/D of rats in sodium aescinate interventional group and medrol interventional group decreased obviously compared with those in oleate model control group. ③ Score of injury of lungs under light microscope (IQA) ; IQA of rats in oleate model control group advanced obviously compared with that in normal control group. IQA of rats in sodium aescinate interventional group and medrol interventional group lowered significantly compared with that in oleate model control group.④ Partial pressure of oxygen in artery (PaO_2) : PaO_2 of rats in oleate model control group lowered significantly compared with that in normal control group. PaO_2 of rats in sodium aescinate interventional group and medrol interventional group improved significantly compared with that in oleate model control group. ⑤ The levels of SOD and MDA in blood plasma and lung tissue:The levels of SOD in plasma and lung tissue of rats in oleate model control group lowered significantly compared with those in normal control group. SOD in plasma and lung tissue of rats in sodium aescinate in-terventional group and medrol interventional group increased significantly compared with that in oleate model control group. The levels of MDA in plasma and lung tissue of rats in oleate model control group lowered significantly compared with those in normal control group. MDA in plasma and lung tissue of rats in sodium aescinate interventional group and medrol interventional group increased significantly compared with that in oleate model control group. Conclusion Sodium aescinate can improve W/D, IQA and PaO_2 by adjusting oxidization of the acute lung injury model of rats, which may provide a possible path for treating acute lung injury in clinical practice.
4.Value of heart rate-blood pressure product of multiplication for identifying compensated shock in children
Haiyan GE ; Shuang LIU ; Jin ZHANG ; Yi HUI ; Wenping GAO ; Yuanyuan SUN ; Chong SHI ; Dong QU
Chinese Journal of Pediatrics 2021;59(12):1074-1079
Objective:To estimate the predictive value of heart rate (HR)-blood pressure (BP) products of multiplication for compensated shock in children.Methods:The study population consisted of 99 children with shock who had lactate measured before receiving vasopressor agents in Department of Critical Care Medicine of Children′s Hospital, Capital Institute of Pediatrics from October 2015 to March 2021. The clinical data including the HR, BP, HR to BP ratio, HR-BP product and lactate at admission and after the correction of shock, as well as the 28-day mortality were collected. According to the outcome at the 28 th day, the patients were divided into survival group and non-survival group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test. Pearson correlation analysis was used to analyze the correlations between lactate and HR, BP, HR to BP ratio and HR-BP product, respectively. Receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive values of HR, BP, HR to BP ratio and HR-BP product for lactate greater than 2 mmol/L. Results:In these 99 children, 49 were males, and the median age was 3.8 (0.7-6.0) years. The most common type of shock was septic shock (61 cases, 62%), followed by cardiogenic shock (12 cases, 12%), hemorrhagic shock (12 cases, 12%), Kawasaki disease shock syndrome (8 cases, 8%) and anaphylactic shock (6 cases, 6%). Sixty-six patients (67%) survived, and 33 patients (33%) died. ROC curve showed that the area under curves (AUC) of lactate (optimal cutoff value 3.15 mmol/L, sensitivity 96.0%, specificity 54.4%, P<0.01) and HR to systolic blood pressure ratio (HR/SBP) (optimal cutoff value 2.0 times/(min·mmHg), sensitivity 62.5%, specificity 69.0%, P = 0.03) for predicting adverse outcome were 0.769 and 0.649, respectively. There were significant correlations between lactate and HR to diastolic blood pressure (DBP) ratio, HR to mean blood pressure (MBP) ratio, SBP, HR/SBP, MBP, DBP and HR ( r= 0.476, 0.452, -0.444, 0.425,-0.410, -0.364, 0.177, all P<0.01), while no significant correlation was found between lactate and the products of HR and BP(all P>0.05). HR/SBP performed better than the other six parameters for predicting lactate>2 mmol/L, with the AUC of 0.872 and the optimal cutoff value of 1.4 bpm/mmHg (sensitivity 92.1%, specificity 70.9%, P<0.01). When MBP was greater than or equal to 65 mmHg, MBP × HR, DBP × HR, SBP × HR, HR, HR/SBP, HR/MBP and HR/DBP were significantly correlated with lactate ( r= 0.706, 0.705, 0.669, 0.626, 0.555, 0.502, 0.446, all P<0.01). And MBP × HR performed better for predicting lactate>2 mmol/L than the other six parameters, with the AUC of 0.974 and the optimal cutoff value of 9446 bpm × mmHg (sensitivity 100.0%, specificity 90.9%, P<0.01). Conclusions:The product of HR and BP, especially the MBP × HR, shows higher predictive values for abnormally elevated lactate in children with compensated shock than the HR/SBP does. It is worth recommending for early identification of compensated shock in children.