1.Effects of matrix metalloproteinase 9 inhibition on the blood brain barrier and inflammation in rats following cardiopulmonary resuscitation.
Zhi-jie HE ; Zi-tong HUANG ; Xiao-tong CHEN ; Zi-jun ZOU
Chinese Medical Journal 2009;122(19):2346-2351
BACKGROUNDNeuroprotective strategies following cardiopulmonary resuscitation (CPR) are an important focus in emergency and critical care medicine. Matrix metalloproteinases (MMPs), especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemia-reperfusion injury after CPR.
METHODSOne hundred and twenty rats were randomly assigned to sham-operated (n = 40), resuscitation treatment (n = 40), and resuscitation control (n = 40) groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation. In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation (ROSC), defined as restoration of supraventricular rhythm and mean arterial pressure (MAP) > or = 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours (n = 8). Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy.
RESULTSIn the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group (P < 0.05). Tissue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group (P < 0.05), they were lower than in the resuscitation control group (P < 0.05).
CONCLUSIONSExpression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.
Animals ; Blood-Brain Barrier ; drug effects ; Brain ; immunology ; ultrastructure ; Cardiopulmonary Resuscitation ; Cytokines ; analysis ; Heterocyclic Compounds, 1-Ring ; pharmacology ; Inflammation ; prevention & control ; Male ; Matrix Metalloproteinase 9 ; analysis ; genetics ; Matrix Metalloproteinase Inhibitors ; Neuroprotective Agents ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Sulfones ; pharmacology
2.A Meta-analysis on the association between adiponectin gene 45T/G/276G/T polymorphisms and type 2 diabetes in Chinese population
Ming-Tong XU ; Xiao-Chao CHEN ; Li-Zi JIN ; Wei-Qing CHEN
Chinese Journal of Epidemiology 2008;29(11):1132-1136
Objective Association between the 45T/G and 276G/T single nueleotide polymorphisms of adiponectin gene and the occurrence of type 2 diabetes in Chinese population was studied. Methods 20 studies consisting 22 ease-control comparisons about 45T/G polymorphism and nine case-control studies about 276G/T polymorphism that were based on our inclusion criterion and available in the literature were reviewed. Results Results from Meta-analysis demonstrated a large heterogeneity among the studies both on 45T/G and 276G/T polymorphisms and a significant association was observed between 45T/G polymorphism at exon 2 of the adiponectin gene and type 2 diabetes among the Chinese population. 45Gallele appeared to be one of the genetic risk factors for susceptibility to type 2 diabetes with a random effects odds ratio ( OR ) of 1.43 ( 95 % CI : 1.17-1.75 ), and the G allele carriers were more susceptible to the disease with an OR of 1.38 ( 95 % CI : 1.04-1.84 ). Results from Meta-analysis, however, showed no association between the 276G/T polymorphism and type 2 diabetes in the Chinese populationr while the random effects OR of the allele 276T to susceptibility of disease was 0.83 (95% CI: 0.61-1.13).Conclusion The current paper on Meta-analysis demonstrated a correlation between the 45T/G single nucleotide polymorphism and the occurrence of type 2 diabetes in Chinese population, which was different from the findings that such an association with 276G/T polymorphism could not be demonstrated in the same ethnic population.
3.Expressions of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death
Liang CHEN ; Hao TANG ; Yan-Bing LIANG ; Zhi-Bin CHEN ; Zhen-Yu LI ; Zi-Tong HUANG ; Long-Yuan JIANG ; Zhong-Fu MA
World Journal of Emergency Medicine 2010;1(2):99-103
BACKGROUND:As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).METHODS:Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.RESULTS:The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].CONCLUSION:The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.
4.Lignans with inhibitory effect on 5α-reductase from Urtica cannabina.
Yan CHEN ; Zi-Xian GUO ; Xiao-Bo LI ; Chen-Jie SUN ; Meng-Yue WANG
China Journal of Chinese Materia Medica 2021;46(15):3846-3852
The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-β-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(trans-urticol-7-O-β-D-glucopyranoside, 7), cycloolivil-4-O-β-D-glucopyranoside(8), isolariciresinol-4'-O-β-D-glucopyranoside(9), and olivil-4'-O-β-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.
5-alpha Reductase Inhibitors
;
Cholestenone 5 alpha-Reductase/pharmacology*
;
Chromatography, High Pressure Liquid
;
Lignans/pharmacology*
;
Magnetic Resonance Spectroscopy
;
Molecular Structure
;
Urticaceae/enzymology*
5.Effect of goblet cell in rat intestine on the restitution process of the gut barrier after hemorrhagic shock.
Jian-xing CHANG ; Shuang CHEN ; Long-yuan JIANG ; Li-ping MA ; Rui-ming CHANG ; Zi-tong HUANG
Chinese Journal of Gastrointestinal Surgery 2005;8(6):510-512
OBJECTIVETo investigate the changes of the goblet cells in the intestine during the restitution process of the gut barrier after hemorrhagic shock.
METHODSForty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into control group (n=7) and experimental group (n=42). Rats in the experimental group was further divided into 6 groups (n=7 each) according to different time point at 1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The specimens from ileum tissue were taken to observe the morphological chan ges of the intestinal mucosa. The number of goblet cells was determined by light microscope and/or electron microscope. The contents of trefoil factor family 3 (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.
RESULTSAfter hemorrhagic shock, mucosal epithelial injury was obvious in the small intestine. Tissue restitution was found after 3 hours, and mostly established after 12 hours. Following tissue restitution,the denuded mucosal surface was covered intensively by goblet cells. The number of goblet cells on the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9 at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the experimental group, the content of TFF3 in the intestinal mucosa increased significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24, P< 0.05).
CONCLUSIONSThe goblet cells play a key role in the restitution of intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal restitution in the early phase.
Animals ; Goblet Cells ; metabolism ; Ileum ; cytology ; Intestinal Mucosa ; cytology ; metabolism ; pathology ; Neuropeptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; metabolism ; Trefoil Factor-3
6.Preparation of transfersomes of vincristine sulfate and study on its prcutaneous penetration.
Yi LU ; Shi-Xiang HOU ; Tong CHEN ; Yi-Yi SUN ; Ben-Xia YANG ; Zi-Yan YUAN
China Journal of Chinese Materia Medica 2005;30(12):900-903
OBJECTIVETo select the best preparation method of vincristine transfersomes (VCR-T) and predict its possibility of being a new formulation of VCR.
METHODOrthogonal design was used to optimize the preparation methods on the basis of single factor pretests; and the permeation tests in vitro were performed in modified Franz diffusion cells.
RESULTThe optimum formula was: pH was equal to 7.3, the ratio of lecithin to sodium deoxycholate is 70/20, the weight of VCR is 10 mg, hydrating time is 30 minutes. The optimized solution was light yellow and transparent colloid solution. The VCR-T are spherical and smooth with average diameters of 94 nm and an encapsulation ratio of 90%. The test in vitro showed that VCR-T could permeat through mouse skin at zero rate with the cumulative penetrating quality amounting to 63.8%.
CONCLUSIONTransfersomes may become a promising carrier of VCR for clinic use.
Administration, Cutaneous ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Deoxycholic Acid ; Drug Carriers ; Hydrogen-Ion Concentration ; Mice ; Particle Size ; Phosphatidylcholines ; Skin Absorption ; Technology, Pharmaceutical ; methods ; Vincristine ; administration & dosage ; pharmacokinetics
7.Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum.
Yi-Yi SUN ; Tong-Hui LL ; Chen-Kang TANG ; Zi-Ping ZHU ; Qun CHI ; Shi-Xiang HOU
China Journal of Chinese Materia Medica 2005;30(11):817-821
OBJECTIVETo study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity.
METHODBCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system.
RESULTD50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection.
CONCLUSIONThe TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Cucurbitaceae ; chemistry ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Excipients ; Liver ; metabolism ; Mice ; Nanostructures ; Particle Size ; Plants, Medicinal ; chemistry ; Rabbits ; Rhizome ; chemistry ; Tissue Distribution
8.Aortic Artery and Cardiac Valve Calcification are Associated with Mortality in Chinese Hemodialysis Patients: A 3.5 Years Follow-up.
Xiao-Nong CHEN ; Zi-Jin CHEN ; Xiao-Bo MA ; Bei DING ; Hua-Wei LING ; Zhong-Wei SHI ; Nan CHEN
Chinese Medical Journal 2015;128(20):2764-2771
BACKGROUNDThis study was to investigate the relationship among aortic artery calcification (AAC), cardiac valve calcification (CVC), and mortality in maintenance hemodialysis (MHD) patients.
METHODSAll MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up for 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay.
RESULTSTotally, 110 MHD patients were involved in this study. Of which, 64 (58.2%) patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 (3.0-225.5) months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 (22.7%) patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause mortality (hazard ratio [HR]: 3.149, P = 0.025) in addition to lower albumin level and lower 25-hydroxy Vitamin D (25(OH)D) level. The presence of CVC was a significant factor associated with cardiovascular mortality (HR: 3.800, P = 0.029) in addition to lower albumin level and lower 25(OH)D level.
CONCLUSIONLateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.
Aortic Diseases ; blood ; complications ; Calcinosis ; blood ; complications ; China ; Female ; Fibroblast Growth Factors ; blood ; Follow-Up Studies ; Heart Valve Diseases ; blood ; complications ; Heart Valves ; pathology ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Renal Dialysis ; mortality
9.Chemical constituents from Urtica dioica fruits.
Wai LI ; Zi-Wei WU ; Xiao-Bo LI ; Yan CHEN ; Meng-Yue WANG
China Journal of Chinese Materia Medica 2022;47(18):4972-4977
The chemical constituents in Urtica dioica fruits were investigated by silica gel chromatography, preparative HPLC, NMR, and HR-MS for the first time. As a result, 21 compounds were isolated from the fruits of U. dioica and identified 7R,8S,8'R-olivil(1), oleic acid(2), α-linoleic acid(3), palmic acid(4), methyl palmitate(5), α-linolenic acid(6), α-linolenic acid methyl ester(7), 5-O-caffeoyl-shikimic acid(8), vanillic acid(9), p-coumaric acid(10), 5-O-p-coumaroylshikimic acid(11), cinnamic acid(12), quinic acid(13), shikimic acid(14), ethyl caffeate(15), coniferyl ferulate(16), ferulic acid(17), caffeic acid(18), chlorogenic acid(19), pinoresinol(20), and quercetin(21). Compound 1 was a new compound and compounds 2-16 were isolated from U. dioica for the first time.
Chlorogenic Acid
;
Fruit
;
Linoleic Acid
;
Oleic Acid
;
Quercetin/chemistry*
;
Quinic Acid
;
Shikimic Acid
;
Silicon Dioxide
;
Urtica dioica/chemistry*
;
Vanillic Acid
;
alpha-Linolenic Acid
10.Effects of Zishen Yutai Pills on endocrine in DOR rats
hua Yao FAN ; Si CHEN ; Jing LI ; Ying ZHAO ; tong Zhi ZHANG ; hui Ying CHEN ; ying Zi LI
Chinese Traditional Patent Medicine 2017;39(11):2249-2254
AIM To study the effects of Zishen Yutai Pills (Codonopsis Radix,Dipsaci Radix,Morindae officinalis Radix,etc.) on endocrine in diminished ovarian reserve (DOR) rats.METHODS Female SD rats with normal oestrous cycle were induced by intragastric administration of 55 mg/(kg · d) tripterygium glycosides for fourteen days to establish DOR model,and then divided into Zishen Yutai Pills high-,low-dose groups,Bujiale group,model control group and negative control group.After 35 days' administration,serum estradiol (E2),follicle-stimulating hormone (FSH),luteinizing hormone (LH) and progesterone (P) levels were detected by ELISA.And ovarian tissue estrogen receptor (ER),follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) expressions were detected by immunohistochemical method.RESULTS Compared with the negative control group,there were significant changes in levels of E2,FSH,LH,P,and expressions of ER,FSHR,LHR in the model control group (P < 0.05),but there were no statistical significances in body weight,ovary index,uterus index and serum FSH/LH level between the two groups (P > 0.05).Compared with the model control group,E2 level was increased in the Zishen Yutai Pills high-,low-dose groups and Bujiale group,FSH,LH levels were decreased,and they also promoted ER expression and restrained FSHR,LHR excessive expressions,which were statistically significant (P < 0.05).P level was significangly increased in different dose groups (P < 0.05),FSH/LH in the high-dose group was obviously decreased (P < 0.05),and body weight,ovary index,uterus index in various intervening groups showed no statistical significances (P > 0.05).CONCLUSION Zishen Yutai Pills can improve ovarian reserve function in DOR rats by affecting the expression of ovarian tissue hormone receptor and regulating endocrine function.