1.Magnetic resonance tracking of transplanted microglia labeled with superparamagnetic iron oxide particles in the brain of normal rat and Alzheimer's disease model rat
Yang SONG ; Yixue XUE ; Lina ZHU ; Yunhui LIU
Chinese Journal of Radiology 2008;(3):314-317
Objective To explore the methods of labeling exogenous microglia with superparamagnetie iron oxide(SPIO)particles,and to monitor the labeled cells after transplantation into the normal rat and Alzheimer's disease(AD)model rat with MR scanning.Methods Microglia was labeled with SPIO particles by using transfection agent,hemagglutinating virus of Japan envelope(HVJ-E).Then the microglias which were labeled with SPIO were injected into the internal carotid artery of normal rat (n=5)and AD model rat(n=5).Three days after transplantation,follow-up serial T2*-weighted gradient-echo MR imaging was performed at 7.0T MRI system.MR images were correlated with histological findings.Results In the brain of normal rat,the labeled microglias were demonstrated as several dotty signalintensity decrease on T2*-weighted MR images.The dotty spots were sporadic around the brain.Histological analysis showed that most prussian blue staining-positive cells were well correlated with the area where a signal intensity decrease was observed in MRI.MR could detect the signal intensity change caused by a few labeled cells.In the brain of AD model rat,MR scan showed a well-defined hypointensity area in the region of Aβ42 iniection.Signal intensity decrease was not obvious in the region of saline injection.The number of iron-positive cells(454±47)/mm2 at sites of Aβ42 injection was much higher than that(83±13)/mm2 of saline injection(P<0.05). Conclusion MR can be used as a non-invasive means of detecting transplanted labeled microglia in vivo,with the potential for future clinical application in cell therapy of AD.
2.Expression of Claudin-5 and ZO-1 in Early Brain Injury after Subarachnoid Hemorrhage in Rats
Duo CHEN ; Jiangwei YUAN ; I_ei SONG ; Xiangtai WEI ; Junhong GUAN ; Yunhui LIU ; Zhihong ZONG
Journal of China Medical University 2010;(9):713-716
Objective Aimed to clarify the molecular mechanism after subarachnoid hemorrhage (SAH) by investigating the expression of tight junction protein Claudin-5 and ZO-1 and the effects of SP600125 on them. Methods Seventy-five male Sprague Dawley rats (300 to 350 g) were randomly divided into sham,SAH,SAH + DMSO (dimethyl sufoxide) solution,SAH +SP600125 (C-Jun N-terminal kinase inhibitor)10 mg/kg,and SAH +SP600125 30 mg/kg groups. The standard endovaseular perforation was performed to produce experimental SAH. The JNK inhibitor SP600125 was intraperitoneally administered at 1 hour before and 6 hours after SAH. Results At 24 hours after SAH,signs of microvessels injury were observed in brain cortex. Compared with the sham group,expression of Claudin-5 and ZO-1 was sig- nificantly decreased (P 〈 0.05 ). JNK inhibitior SP600125 suppressed the decrease of Claudin-5 and ZO-1 expression, attenuated blood-brain barrier disruption in rats after SAH. Conclusions The blood-brain barrier disruption is an important mechanism of early brain injury after SAH. JNK inhibitor SP600125 improves neurological outcomes and provides neuropmtecfion against acute events after SAH such as bloodbrain barrier disruption and cell apoptosis.
3.Association between osteoprotegerin gene polymorphisms and severe pre-eclampsia in Chinese women
Yan YANG ; Yunhui GONG ; Shanshan NI ; Bin ZHOU ; Yaping SONG ; Lin ZHANG ; Rong ZHOU
Chinese Journal of Obstetrics and Gynecology 2012;47(1):24-28
Objective To investigate the potential association between 163A/G and 950T/C polymorphisms of osteoprotegerin(OPG)gene and severe pre-eclampsia.Methods Eighty-five severe preeclamptic patients and 81 normal term pregnant women(as control group)were recruited from the Department of Obstetrics and Gynecology,West China Second University Hospital,Sichuan University during the period from July 2007 to March 2009,and they were all Han population living in Chengdu,China.Genotype and allele frequencies of 163A/G and 950T/C were determined by the PCR-restriction fragment length polymorphism(RFLP)assay.Clinical and biochemical parameters for different alleles between the patients and controls were compared for statistical significance respectively,such as blood pressure,serum creatinine and 24-hour urine protein.Results The observed and expected genotype counts were consistent with Hardy-Weinberg equilibrium.No significant differences were found in the genotype and allele frequencies of 163A/G and 950T/C polymorphisms between the two groups(P > 0.05).However,in the preeclamptic group,serum creatinine was significantly higher in women with the AG + GG genotypes [(76 ±24)μmol/L]compared with AA genotype[(56 ± 18)μmol/L].Reversely,birth weight was lower in the AG + GG genotypes[(2040 ± 721)g]than those in the AA genotype[(2520 ± 810)g],and the P <0.05,respectively.In the severe pre-eclampsia,950T/C TT genotype carriers exhibited significantly higher systolic blood pressure[(153 ± 16)mm Hg(1 mm Hg =0.133 kPa)]and 24-hour urine protein [(4.0±2.5)g]compared with TT + TC carriers[(145 ±17)mm Hg,(2.9±1.8)g],respectively,furthermore the P < 0.05.Conclusions In severe pre-eclampsia,carriers with G allele at position 163A/G has more genetic predisposition than A allele carriers,as well as 950T/C T allele carriers compared with C carriers.Taken together,this study suggested that OPG gene polymorphisms might be associated with some clinical parameters of severe pre-eclampsia.
4.Early onset of group B streptococcal sepsis in newborn: clinical analysis of 27 cases
Limin ZHU ; Yanping ZHANG ; Xiangyong KONG ; Zhichun FENG ; Changshuan YANG ; Yunhui SONG
Chinese Journal of Neonatology 2019;34(1):38-41
Objective To study the clinical features of early-onset Group B streptococcal(GBS) sepsis to improve the management of early-onset GBS sepsis.Method To review the clinical data of 27 cases of early-onset GBS sepsis in the Hospital over the past 5 years (January 2013 to November 2017),and analyze its clinical features,laboratory results,complications,prognosis and perinatal characteristics.Result A total of 27 cases of early-onset GBS sepsis were enrolled within 5 years,accounting for 0.85‰ (27/31 936) of total hospitalized patients over the same period.Among them,6 were premature infants and 21 full-term infants.The time of onset was within 24 hours.In all the cases,except for one full-term infant with fever as the initial symptom,the remainder had dyspnea as the initial symptom,accompanied by poor response and low poor muscle tone.Among them,17 patients required assisted ventilation.One of the full-term infant treated with ECMO within 48 hours after birth because of dyspnea,pulmonary hypertension and persistent hypoxemia,etc.,and improved and discharged;another 10 patients needed hood oxygen supply.5 cases (18.5%,5/27) diagnosed with purulent meningitis.In complete blood count,white blood cells ranged from (0.8~34.2)× 109/L,the minimum platelets counts was 16× 109/L,the maximum CRP was 249 mg/L,and maximum procalcitonin was> 100 ng/ml.All blood cultures were sensitive to penicillin.of the 27 patients,2 died despite of medical treatment,and 5 patients died as their parents worried about possible sequelae and discharged against medical advice.Therefore,tlhe total mortality rate was 25.9% (7/27).All children were administered penicillin after the blood culture results were known,meropenem was subsequently added or replaced with vancomycin according to the clinical progress of the child.The remaining 20 patients recovered and discharged.Conclusion The clinical manifestation of early onset GBS septicemia is critically ill,with early onset,rapid progress,and high mortality.Special attention should be paid to high-risk cases during perinatal period,and early recognition with effective treatment would reduce morbidity and mortality.
5.Activation of Nrf2/HO-1/NQO1 Signaling Pathway by Shenqi Tangluo Pill Improves Oxidative Stress Injury of Skeletal Muscle of Type 2 Diabetes Mellitus Mice
Xiaoli PEI ; Yonglin LIANG ; ⁎ ; Yongqiang DUAN ; ⁎ ; Xiangdong ZHU ; Bing SONG ; Min BAI ; Yunhui ZHAO ; Sichen ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):131-139
ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill (SQTLP) on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus (T2DM) mice based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway. MethodA total of 60 7-week-old male db/db mice [specific pathogen-free (SPF) grade] were selected and fed for one week for adaption. They were divided into the model control group, SQTLP low-, medium- and high-dose (19, 38, and 76 g·kg-1) groups and metformin group (0.26 g·kg-1) by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose (FBG) was detected. Fasting serum insulin (FINS) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment-insulin resistance (HOMA-IR) index and the homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) in skeletal muscle tissue were detected by immunofluorescence (IF). The expression levels of Nrf2, HO-1, NQO1 and glutamate-cysteine ligase catalytic subunit (GCLC) proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group, FBG, FINS and HOMA-IR in the model group were significantly increased (P<0.05), while HOMA-ISI was decreased (P<0.05). The results of OGTT and ITT showed that blood glucose was significantly increased at all time points (P<0.05), and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased (P<0.05), and MDA and NADPH contents were significantly increased (P<0.05). In skeletal muscle tissues, the arrangement of muscle fibers was loose, the nucleus was disordered, and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly decreased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the metformin group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points (P<0.05). The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly increased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased (P<0.05), and the NADPH content was decreased (P<0.05). The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05). Compared with those in the SQTLP low-dose group, FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05) in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice, and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway, promoting the expression of antioxidant enzymes, and thus improving the oxidative stress injury in the skeletal muscle.