Role of CypD-mediated mPTP in melatonin improving cognitive impairment induced by repeated exposure to sevoflurane / 中国药理学通报

Aim To investigate the involvement of cy-clophilin D ( CypD ) -mediated mitochondrial permeability transition pore ( mPTP) in the neuroprotective effects of melatonin on cognitive impairment induced by repeated exposure to sevoflurane in newborn animals. Methods Mice were randomly assigned into control group, sevoflurane ( Sevo) group, and melatonin pre-treatment + sevoflurane ( Sevo + Mel) group. JC-1 kit was used to assess the mitochondrial membrane potential ( MMP) ; Western blot analysis was used to evaluate the protein expressions of CypD, postsynaptic density protein 95 ( PSD95 ), and Synapsin-1; and behavioral test were employed to measure cognitive function. Results The MMP level in the Sevo group was significantly reduced compared to the control group (P < 0. 01 ), the expression of CypD increased (P <0. 05), whereas the expression of PSD95 and Synapsin-1 decreased ( P < 0. 01) . Furthermore, the new object recognition index and spatial memory ability both exhibited a significant decline (P < 0. 01, P < 0. 05). However, when compared to the Sevo group, Sevo + Mel group could raise the MMP level (P <0. 01), increase the expression of synaptic proteins ( P < 0. 05 ), decrease the expression of CypD (P <0. 01) and elevate the new object recognition index and the spatial memory capacity ( P < 0. 01 ). Conclusions Melatonin could ameliorate cognitive impairment induced by repeated exposure to sevoflurane in newborn mice, and the underlying mechanism may be attributed to the inhibition of mPTP mediated by CypD and the promotion of synaptic protein synthesis.

Advances of using antibody against B cell activating factor for treatment of autoimmune diseases / 生物工程学报

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.

Study on the mechanism of Wuzi-Yanzong-Wan-medicated serum interfering with the mitochondrial permeability transition pore in the GC-2 cell induced by atractyloside / 中国天然药物

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.

Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion / 华西口腔医学杂志

OBJECTIVES@#To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells.@*METHODS@#A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay.@*RESULTS@#The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (@*CONCLUSIONS@#The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.

The interaction between Cyclophilin A and CD147 and its clinical significance in periodontal diseases / 口腔疾病防治

@#Cyclophilin A (CypA) is the first foldable enzyme in human cells that has peptidyl proliferase-trans isomerase activity and has a strong proinflammatory effect. CD147 can act as the signal receptor of CypA. The interaction of the two through cell-surface heparin binding activates extracellular regulated protein kinases (ERK1/2) and nuclear factor kappa-B (NF-κB) signaling pathways in macrophages and increases the expression of MMPs and other inflammatory factors. The CypA/CD147 interaction regulates inflammation, promotes the inflammatory response and bone resorption and is involved in the pathological processes of a variety of systemic diseases. CypA and CD147 may take part in the chemotaxis of inflammatory cells, increase white blood cell infiltration in tissues, and increase CypA and CD147 expression in periodontitis gum tissue and gingival groove liquid with inflammation, prompting their interaction to promote the progression of periodontitis. However, the specific function of the signaling pathways in the periodontitis mechanism still requires further elucidation.

Role of cyclophilin A during coronavirus replication and the antiviral activities of its inhibitors / 生物工程学报

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.

Correlation between content of saikosaponin and expression of key enzyme genes in different parts of Bupleurum chinense / 中草药

Objective: To select reference genes suitable for the expression analysis of Bupleurum chinense, and analyze the relationship between the content of saikosaponin and the gene expression of key enzymes in different tissues of B. chinense. Methods The roots, stems, leaves and fruits of B. chinense were used as test materials, and five commonly used internal reference genes of Actin, α-tubublin, β-tubulin, Cyclophilin and EF-1α were selected as candidates by real-time quantitative PCR. Based on the selected internal reference gences, tissue expression pattern of ACAT, FPS, HMGR, IPPI, PMD, PMK, SE, SS, β-AS, UGT1, UGT3, UGT6, UGT8, UGT10, P450-7 and P450-12 genes in B. chinense was analyzed. The content of saikosaponin a, saikosaponin c and saikosaponin d were determined by HPLC, and correlation analysis was performed by SPSS. Results:The EF-1α gene with the best stability in the five candidate genes (EF-1α, Cyclophilin, Actin, β-tubulin, α-tubublin) was selected as the internal reference gene. The expression levels of 16 key enzymes in the roots of B. chinense were measured. The results showed that ACAT, PMK, IPPI, SS, SE, UGT1, UGT3, UGT6, and UGT8 were the highest in the aboveground parts, the levels of HMGR, β-AS, P450-7 and P450-12 were higher in the roots than those in the aboveground parts, but PMD, FPS and UGT10 were not significantly different in the tissues. The content of saponins in the root was much higher than that in the aerial parts (stem, leaf and fruit) by HPLC. The results of correlation analysis showed that 16 key enzyme genes in the upstream ACAT, HMGR, PMD, SE and so on were significantly correlated with downstream P450-7, P450-12, UGT3, UGT6 and UGT8 (P < 0.05). It showed that the key enzyme genes were closely related to each other and regulated the synthesis of saikosaponin in common. The correlation analysis between the 16 key enzyme genes and the content of saikosaponin showed: HMGR, P450-7, p450-12 and the total of three saponins were significantly positively correlated (P < 0.01), and β-AS was significantly correlated with the total content of three saponins (P < 0.05), and HMGR, P450-7, P450-12, and β-AS were significantly correlated with the monomer saponins a, c, d (P < 0.05). These four genes jointly regulated the synthesis of saikosaponin and had an important effect on the accumulation of saponin. Conclusion:The HMGR, β-AS, P450-7 and P450-12 genes in the saikosaponin synthesis pathway have a consistent distribution in saikosaponin synthesis and play an important role in the regulation of saponin synthesis.

Effect of extracellular cyclophilin A on inflammatory response and anti-inflammatory activity of antibody against cyclophilin A / 生物工程学报

Cyclophilin A (CypA) is a member of peptidyl prolylisomerases (PPIase) family. CypA is best known as a ubiquitously distributed intracellular protein. It has also been shown to be secreted by cells in response to inflammatory stimuli and oxidative stress. Extracellular CypA (eCypA) interacts with CD147 to initiate inflammatory responses via recruiting leucocytes into inflamed tissue. Recombinant CypA was expressed in Escherichia coli and then purified using Superdex 75™ 16/60. The results of Real-time PCR and ELISA showed that the expression levels of proinflammatory cytokines, such as IL-1β, secreted by eCypA stimulated BMDM were significantly up-regulated, indicating that eCypA played an important role in promoting inflammatory responses. In addition, anti-CypA antibody was prepared using purified CypA protein for therapeutic evaluation in a mouse model of LPS-induced acute lung inflammation. Antibody-treated mice showed reduced lung injury and the expression levels of IL-1β in the lung tissue and blood were decreased significantly, indicating that anti-CypA antibody exerted a potent anti-inflammatory activity. Our findings provide a potential therapeutic antibody for inflammation-mediated diseases.

Expression of cyclophilin A in foaming of macrophages induced by silica / 中国职业医学

OBJECTIVE: To investigate the role of cyclophilin A in the foaming process of macrophages induced by free silica( SiO_2). METHODS: The human peripheral blood mononuclear cell THP-1 in the logarithmic growth phase was induced and differentiated into human macrophages with phorbol 12-myristate 13-acetate at 100 μg/L for 48 hours. The cells were divided into 4 groups. The cells in the blank control group were not treated. The cells in the oxidized low-density lipoprotein( ox-LDL) control group were treated with a final concentration of 50 mg/L ox-LDL. The cells of 50 mg/L SiO_2 group were treated with 50 mg/L of SiO_2 and ox-LDL. The cells of 100 mg/L SiO_2 group were treated with 100 mg/L of SiO_2 and 50 mg/L of ox-LDL. After treatment of cells for 48 h,cell viability was measured by MTS method. The lipid accumulation of cells was observed by oil red O staining and colorimetric method; the expression of cyclophilin A in cell supernatant was detected by enzyme-linked immunosorbent assay,and the expression of cyclophilin A in the cells was detected by Western blotting. RESULTS: The cell viability was the highest when the concentration of SiO_2 was 100 mg/L compared with the control and other four SiO_2groups( P < 0. 01). The cell foaming change in the 100 mg/L SiO_2 group observed by oil red O staining significantly increased compared with the blank control group. The expression of total cholesterol,free cholesterol increased in the ox-LDL control group,50 mg/L SiO_2 group and 100 mg/L SiO_2group( P <0. 05),and the cholesterol specific gravity increased( P < 0. 05) compared with the blank control group,meanwhile the expression of cyclophilin A in the cell supernatant increased( P < 0. 05),and the expression in the macrophages cells decreased( P < 0. 05). CONCLUSION: Cyclophilin A is involved in the foaming process of macrophages induced by SiO_2.

Mass Spectrometric Analysis of Proteoforms of Cyclophilin A from Human Colorectal Carcinoma Tissues / 分析化学

Cyclophilin A was isolated from human colorectal carcinoma tissues by ultrafiltration,affinity chromatography,and two dimensional electrophoresis.By the aid of Western blot analysis,several isoforms of cyclophilin A were detected.,The tryptic digests from cyclophilin A were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry as well as electrospray tandem mass spectrometry techniques.Several different modifications such as N-terminal acetylation (Ac-1Met and Ac-2Val) and phosphorylation of 5Thr were identified from these isoforms of cyclophilin A,which represented the majority of the proteoforms of cyclophilin A in this study.In addition,other kinds of modifications such as oxidation and deamidation were also found in these proteoforms.The results indicated that the developed method could be used to rapidly and correctly identify the several proteoforms of cyclophilin A isolated from human colorectal carcinoma tissues.

Effects of Tongxinluo Capsules on Serum CyPA and MMP-9 Levels in Patients with Coronary Heart Disease after PCI / 中国药房

OBJECTIVE:To investigate the effects of Tongxinluo capsules on the levels of serum cyclophilin A (CyPA) and matrix metalloproteinase-9 (MMP-9) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).METHODS:A total of 115 CHD patients undergoing PCI were randomly divided into control group (59 cases) and observation group (56 cases).Control group was given conventional treatment.Observation group was additionally given Tongxinluo capsules 0.78 g,3 times a day,for consecutive 6 months,on the basis of control group.The levels of CyPA and MMP-9 as well as the occurrence of ADR were observed in 2 groups before and after treatment.RESULTS:Before treatment,there was no statistical significance in serum level of CyPA and MMP-9 between 2 groups (P＞0.05).The levels of CyPA in 2 groups 1 d and 1 month after surgery as well as the level of CyPA in control group 6 months after surgery were all significantly higher than before surgery,but the observation group was significantly lower than the control group 1 and 6 months,this index was decreased gradually as time,with statistical significance (P＜0.05).There was no statistical significance in the levels of CyPA between 2 groups 1 d after surgery or in observation group between 6 months after surgery and before surgery (P＞0.05).The levels of MMP-9 in 2 groups 1 d and 1 month after surgery were significantly higher than before surgery,and the observation group was significantly lower than the control group,this index was decreased gradually as time,with statistical significance (P＜0.05).There was no statistical significance in the levels of MMP-9 of 2 groups between 6 months after surgery and before surgery(P＞0.05).There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Based on routine treatment,Tongxinluo capsules can significantly reduce the levels of CyPA and MMP-9 in CHD patients after PCI.

Prokaryotic clone, expression and immunological analysis of recombinant Schistosoma japonicum cyclophilin B / 国际检验医学杂志

Objective To clone and express Schistosoma j aponicum cyclophilin B (SjCyPB) gene in E.coli,and to identify and analyze the immunity of recombinant proteins.Methods A pair of specific primers was designed according to GenBank of Schistosoma japonicum sequence.SjCyPB gene was amplify by PCR and then connected to pET28 vector.The recombinant plasmid pET28a (+)-SjCyPB was constructed and transformed into E.coli BL21 cell line,the recombinant plasmid was identified by double enzyme digestion and sequence analysis.After induced by isopropyl-B-D-thiogalaetoside (IPTG),the expressed recombinant proteinwas purified by affinity-chromatography,and then verified by Western blotting.Rats were immunized recombinant SjCyPB,andthe SjCyPB-specific IgG was detected by ELISA.Results SjCyPB gene was successfully inserted into pET28a(-) vecter which identified by double enzyme digestion and sequence analysis.Recombinant SjCyPB protein was highly expressed in E.coli.The Western Blotting analysis confirmed that the recombinant protein could specifically combine to S.japonicum-infected rabbit serum.Using recombinant protein to immunize rats,the SjCyPB-specific IgG antibody titer was 1 ∶ 51 200 detected by ELISA.Conclusion The recombinant SjCyPB is successfully constructed,and recombinant SjCyPB has immunogenicity and antigenicity.

Regulatory necrosis:a novel way to recognize and prevent injury-relevant diseases / 中国药理学通报

Necrosis is also tightly controlled by signaling path-ways,thus it is called as regulated necrosis,which includes ne-croptosis,ferroptosis,parthanatos and CypD-mediated necrosis. It has been shown that regulated necrosis is closely related to the occurrence,development and prognosis of injury-relevant disea-ses such as myocardial infarction,stroke,neurodegenerative dis-eases.It will be significant for prevention and therapy of injury-relevant diseases to clarify the signal transductions and regulatory mechanisms for the regulated necrosis.

Role of cyclophilinD in induction of the regulated necrosis / 基础医学与临床

CyclophilinD ( CypD) , a member of cyclophilins family displays a variety of biological function .CypD lo-cates in the mitochondrial matrix .As an component of mitochondrial permeability transition pore ( mPTP ) , CypD plays an important role in the regulating of mPTP opening , which leads to mitochondrial dysfunction and CypD-de-pendent regulated necrosis .Elucidation of the mechanisms of CypD in regulating mPTP and the regulated necrosis will provide novel insights in injury-relevant diseases , such as cardiac or cerebral ischemia .

Selective targeting p53WT lung cancer cells harboring homozygous p53 Arg72 by an inhibitor of CypA / 中国药理学与毒理学杂志

OBJECTIVE To explored the potential of pharmacological stabilization and reactivation of p53 for targeted cancer therapies. METHODS The cytotoxicity of a potent Cyclophilin A (CypA) inhibitor HL001 was tasted against a panel of cancer cell lines. The genotypes and activation of p53 were compared with the cytotoxicity profile of HL001. Two-dimensional (2D) PAGE analysis was performed to investigate differentially expressed proteins that involves in the anti-proliferation effects of HL001. Pull-down and Co-IP were used to confirmed the new identified PPI between CypA and G3BP1 and orthotopic animal model of lung cancer was used to tested the anti- tumor activity of HL001 in vivo. RESULTS We identify a novel CypA small molecule inhibitor HL001 that induces non-small cell lung cancer (NSCLC) cell cycle arrest and apoptosis via restoring p53 expression. We find that HL001 stabilizes p53 through inhibiting the MDM2-mediated p53 ubiquitination. Further mechanistic studies reveal that the downregulation of G3BP1 and the induction of reactive oxygen species and DNA damage by HL001 contribute to p53 stabilization. Surprisingly, HL001 selectively suppresses tumor growth in p53 wildtype NSCLC harboring Arg72 homozygous alleles (p53- 72R) through disrupting interaction between MDM2 and p53-72R in a CypA dependent manner. Moreover, combining HL001 with cisplatin synergistically enhance tumor regression in orthotopic NSCLC mouse model. CONCLUSION Pharma?cologic inhibition of CypA offers a potential therapeutic strategy via specific activation of p53-72R in NSCLC.

Expression of cyclophilin A in gastric cancer and its relationship with proliferation of gastric cancer cells / 第二军医大学学报

Objective To examine the expression of cyclophilin A (CypA) in gastric cancer tissues and cell lines, and to explore the effect and mechanism of CypA on the proliferation of gastric cancer cells. Methods Real-time quantitative PCR and Western blotting analysis were used to detect the expression of CypA in gastric cancer tissues, the corresponding adjacent tissues and gastric cancer cell lines. Small interfering RNAs targeting CypA were synthesized and transfected into the gastric cancer cell line MKN45. The effect of CypA-siRNA on endogenous CypA expression was observed; meanwhile, nonspecific siRNA control group and negative control group were also designed. Cell proliferation was measured with MTT assay in each group; cell cycle was detected with flow cytometry. The expression of PCNA, P21, P16, and CyclinD1 gene, involved in cell proliferation, were also detected by real-time quantitative PCR and Western blotting analysis. Results CypA expression was significantly up-regulated in gastric cancer tissues compared with para-cancer tissues; and CypA expression in gastric cancer cell lines was also significantly higher than that in the gastric epithelial cell line GES-1, with the highest expression found in the poorly-differentiated gastric cancer cell line MKN45(P<0. 05). The expression of CypA was significantly inhibited by the CypA-siRNA in MKN45 (P<0. 05). MTT assay showed that the inhibition of CypA by CypA-siRNA significantly suppressed MKN45 cell proliferation (P<0. 05). The ratio of G0/G1 phase cells was significantly increased in MKN45 cells after CypA-siRNA transfection, while the ratio of G2/M phase was significantly decreased (P<0. 05). In addition, the expression of PCNA, Cyclin D1 was significantly decreased at mRNA and protein levels when CypA was inhibited, and the expression of P21 was significantly increased (P<0. 05). Conclusion CypA is overexpressed in gastric cancer cells; CypA gene can effectively promote gastric cancer cell proliferation by regulating some proliferation related genes.

In silico cloning and bioinformatics analysis of cyclophilin from Lotus corniculatus / 中草药

Objective: Using electronic cloning technology to predict cyclophilin gene of Lotus corniculatus. Methods: Using glycine max cyclophilin sequence as probe sequence, based on EST sequence from NCBI and assembled by CAP3 sequence assembly programme, using bioinformatic database and related software, the structure prediction and function analysis were performed. Results: The full length of cyclophilin gene was 1 346 bp, it contained a 771 bp ORF, encoding 256 amino acids, and the protein was a hydrophilic protein. Conclusion: The study is intended to further explain the molecular genetic function theory and experimental basis.

Mechanism of Cyclophilin A in tumor / 国际肿瘤学杂志

Cyclophilin A (CypA) is found to be highly expressed in different kinds of tumor cells,which could regulate the occurrence and development of many kinds of tumor through multiple signal transduction pathways such as inducing the formation of inflammatory carcinoma,accelerating the transcription cycle of tumor cells,promoting the invasion and metastasis of tumor cells,inhibiting the apoptosis of tumor cells and reducing the sensitivity of tumor cells to chemotherapy drugs.It suggests that CypA might be considered as a kind of oncogene,which is expected to be a novel target for tumor treatment.

Endothelial-dependent Vasodilatation and Expressions of CyPA, p-ERK1/2 in Experimental Rats With Obesity Combining Atherosclerosis / 中国循环杂志

Objective: To observe the endothelial-dependent vasodilatation and expressions of cyclophilin A (CyPA), phosphorylated extracellular signal regulated kinase1/2 (p-ERK1/2) in experimental rats with obesity combining atherosclerosis. Methods: A total of 30 male Wistar rats were randomly divided into 3 groups:Control group, the rats received basic diet followed by intraperitoneal injection of normal saline;Atherosclerosis (AS) group, the rats received basic diet for 8 weeks followed by high cholesterol diet with intraperitoneal injection of a single dose vitamin D3 600,000 IU/kg; Obesity+AS group, the rats received high cholesterol diet for 8 weeks (which made their body weights at 20%higher than the other 2 groups) followed by intraperitoneal injection of a single dose vitamin D3 600,000 IU/kg. n=10 in each group. 16 weeks later, the endothelial-dependent vasodilatation was examined in all rats, expressions of CyPA and p-ERK1/2 in arterial wall were detected by HE staining and immunohistochemistry. Results: Compared with Control group, both AS group and Obesity+AS group had reduced endothelial-dependent vasodilatation (72.49 ± 3.27)%and (42.28 ± 2.62)%vs (96.63 ± 3.85)%, such reduction was even more in Obesity+AS group (42.28 ± 2.62)%vs (72.49 ± 3.27)%, all P Conclusion: The rats with obesity and AS had decreased endothelial-dependent vasodilatation, severe atherosclerosis and calciifcation plaques, increased expressions of CyPA and p-ERK1/2, which speculated that obesity might be an independent risk factor for atherosclerosis.

Relationship Between Blood Levels of Cyclophilin A and Chronic Heart Failure / 中国循环杂志

Objective: To explore the relationship between blood levels of cyclophilin A (CyPA) and chronic heart failure (CHF). Methods: A total of 166 CHF patients were enrolled as CHF group, according to NYHA classiifcation, it was further divided into 4 sub-groups: Class I,n=37, Class II,n=39, Class III,n=46 and Class IV,n=44. In addition, there was a Normal control group,n=52. Blood levels of CyPA, B-type natriuretic peptide (BNP) and high sensitivity C-reactive protein (hs-CRP) were examined and compared among different groups. Results: Compared with Normal control group, CHF group had elevated CyPA (5.11 ± 2.43) ng/ml vs (2.28 ± 0.61) ng/ml, BNP (385.65 ± 184.06) pg/ml vs (90.37 ± 18.44) pg/ml and hs-CRP (11.74 ± 5.44) mg/L vs (5.99 ± 1.14) mg/L, all P0.05. Pearson correlation analysis indicated that blood levels of CyPA were positively related to BNP and hs-CRP in CHF patients (r=0.838,P Conclusion: Blood levels of CyPA were elevated in CHF patients and it’s obviously related to NYHA classiifcation, which might have certain effects on CHF diagnosis and evaluation.