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Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.
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Objective:To investigate the expression of Piezo1 in small intestinal mucosal epithelial cells of patients with Crohn′s disease (CD) and its clinical correlation with CD.Methods:From January 1st 2010 to November 30th 2020, the clinical data including age, gender, disease location and biological behavior, etc of 57 patients with CD (CD group) who underwent surgery at The First Affiliated Hospital of Anhui Medical University were retrospectively. And at same time the normal samll intestinal epithelial tissues of 10 healthy individuals who underwent colonoscopy were collected as the healthy control group. The expression of Piezo1 in small intestinal epithelial cells of CD patients with different disease sites, biological behavior and disease activity were detected by immunofluorescence staining and hematoxylin-eosin staining. The histological score system and intestinal fibrosis score were used to analyze the inflammation and fibrosis of the intestinal tissues of patients with CD. Semi-quantitative analysis of Piezo1 in small intestinal epithelial cells was analyzed by ImageJ software. And the correlation between Piezo1 expression and clinical characteristics and pathological features of small intestine was also analyzed. Independent sample t test and analysis of variance were used for statistical analysis. Results:In CD group, there were 37 males (64.9%) and 20 females (35.1%). The age was (39.1±14.2) years old, ranged from 18 to 71 years old, and the average duration of the disease was (26.5±24.1) months. There were 29 cases (50.9%)of ileal type, 26 cases (45.6%) of ileocolonin type and 2 cases (3.5%) of colonic type. There were 12 cases (21.1%) of non-penetrating non-stenotic type, 31 cases (54.4%) of stenotic type and 14 cases (24.6%) of penetrating type. There were 47 cases (82.5%) with moderate activity and 10 cases (17.5%) with severe activity. There were 17 cases (29.8%) of moderate intestinal inflammation, 40 cases (70.2%) of severe intestinal inflammation. The score of intestinal fibrosis in six cases (10.5%) was 1, 28 cases (49.1%) was 2, 18 cases (31.6%) was 3, five cases was 4. The relative expression level of Piezo1 in intestinal mucosal epithelial cells of CD group was higher than that of healthy control group (12.9±4.6 vs. 8.5±1.1), the relative expression of Piezo1 in intestinal mucosal epithelia cells of stenotic type and penetrating type CD patients were both higher than that of non-penetrating and non-stenotic CD patients (12.6±3.8 and 9.8±2.4 vs. 6.0±1.3), and the differences were all statistically significant ( t=3.00, -3.66 and -3.32, all P<0.01). The relative expression of Piezo1 in small intestinal epithelial cells of CD patients with severe intestinal inflammation was higher than that of CD patients with moderate intestinal inflammation (13.1±4.0 vs. 9.7±3.1), and the difference was statistically significant ( t=-2.65, P<0.05). The relative expression levels of Piezo1 in small intestinal epithelial cells of patients with intestinal fibrosis score of 4, 3, 2 and 1 were 17.6±5.2, 12.6±1.7, 9.1±2.1 and 5.8±1.1, respectively; the relative expression levels of Piezo1 in intestinal epithelial cells of patients scored 4 were higher than that of patients scored 3, 2 and 1, and that of patients scored 3 was higher than patients scored 2 and 1, and that of patients scored 2 was higher than that of patients scored 1, and the differences were all statistically significant ( t=-2.98, -5.10, -3.84, 4.60, 6.55 and 2.56, all P<0.05). The relative expression of Piezo1 in intestinal mucosal epithelial cells was related to the severity of intestinal inflammation and fibrosis. The more severe the intestinal inflammation and fibrosis, the higher the relative expression of Piezo1 in intestinal mucosal epithelial cells. Conclusions:The relative expression of Piezo1 in small intestinal epithelial cells is related to the biological behavior and the severity of intestinal inflammation and fibrosis of CD. It is speculated that the expression of Piezo1 in small intestinal epithelial cells may be clinically related to the process of intestinal wall fibrosis in CD to some extent, however whether it plays an important role in the process of intestinal wall fibrosis in CD and its specific mechanism need to be further studied.
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Objective:To investigate the mechanism of Shugan Bushen Yulin decoction in inhibiting voltage-dependent anion-selective channel protein 2 （VDAC2） gene methylation， affecting sperm mitochondrial function， and improving sperm motility through the cyclic adenosine monophosphate/protein kinase A （cAMP/PKA） pathway. Method:Forty male SD rats were randomly divided into the blank group， model group， high- and low-dose Shugan Bushen Yulin decoction groups， and L-carnitine group， with eight rats in each group. Adenine （0.05 g·kg<sup>-1</sup>） was administered by gavage for 14 d for inducing oligospermia and asthenospermia. Rats in the Shugan Bushen Yulin decoction groups were treated with intragastric administration of 32.4， 8.1 g·kg<sup>-1 </sup>Shugan Bushen Yulin decoction， respectively， while those in the L-carnitine group received 0.27 g·kg<sup>-1</sup> L-carnitine by gavage. Following the measurement of sperm motility using an automatic sperm analyzer， the pathological changes in testicular tissue were observed by hematoxylin-eosin （HE） staining. Sperm mitochondrial membrane potential was detected by flow cytometry. The expression of VDAC2 in the testicular tissue was determined by immunofluorescence assay. Real-time polymerase chain reaction （Real-time PCR） was conducted for detecting VDAC2 mRNA expression in testicular tissue. The methylation of VDAC2 gene was examined using bisulfite sequencing. The cAMP expression in testicular tissue was detected by enzyme-linked immunosorbent assay （ELISA）， and the PKA protein expression in testicular tissue by Western blot. Result:Compared with the blank group， the model group exhibited significantly decreased sperm density and motility （<italic>P</italic><0.01）， increased mitochondrial membrane potential （<italic>P</italic><0.01）， down-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in testicular tissue （<italic>P</italic><0.01）， and elevated VDAC2 gene methylation （<italic>P</italic><0.01）. Compared with the model group， L-carnitine and Shugan Bushen Yulin decoction at the high and low doses all remarkably increased the sperm density and motility and mitochondrial membrane potential （<italic>P</italic><0.01）， up-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue （<italic>P</italic><0.01）， and lowered the methylation of VDAC2 in testicular tissue （<italic>P</italic><0.01）. The comparison with the L-carnitine group showed that the sperm density and motility and mitochondrial membrane potential in the low-dose Shugan Bushen Yulin decoction group declined significantly （<italic>P</italic><0.01）. The VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue were significantly down-regulated （<italic>P</italic><0.01）， while the methylation of VDAC2 was significantly enhanced （<italic>P</italic><0.01）. Conclusion:Shugan Bushen Yulint decoction may inhibit VDAC2 gene methylation， increase VDAC2 expression， regulate cAMP/PKA pathway， and change mitochondrial membrane potential to enhance the sperm motility.
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AIM:To investigate the interaction of Ca 2+-sensing proteins , stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), in Ca2+-sensing receptor (CaSR)-mediated extracellular Ca2+ influx and production of nitric oxide ( NO).METHODS: Human umbilical vein endothlial cells (HUVECs) were incubated with CaSR agonist spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels ( ROC) ] alone or combined with CaSR negative allosteric modulator Calhex 231+ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro 31-8220, or PKCα/β1 selective inhibitor Go 6976 (activate SOC, blocking ROC).The protein expression of STIM1 and Orai1 was determined by the method of immu-nofluorescence .The interaction between STIM 1 and Orai1 was examined by co-immunoprecipitation .The second to third passages of HUVECs were divided into STIM 1 and Orai1 short hairpin RNA group ( shSTIM1+shOrai1 group ) , vehicle-STIM1+vehicle-Orai1 group and control group , and then incubated with the 4 different treatments above .The intracellular Ca2+concentration ( [ Ca2+] I ) was detected using the fluorescent Ca 2+indicator Fura-2/AM.The production of NO was also determined by DAF-FM DA fluorescent probe .RESULTS:The protein expression of STIM 1 and Orai1 was located in the cytoplasm.Compared with control group , the localization of STIM1 and Orai1 in the cytoplasm was reduced after the HUVECs were incubated with Calhex 231+TPA, Ro 31-8220 or Go 6976, and the interaction of STIM1 and Orai1 was de-creased significantly .The [ Ca2+] I and the net NO fluorescence intensity in shSTIM 1+shOrai1 group were significantly re-duced after the 4 different treatments (P<0.05).CONCLUSION:STIM1 and Orai1 are components of SOC and ROC in store-and receptor-operated Ca 2+entry and NO generation .
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AIM:To investigate the interaction of Ca 2+-sensing proteins , stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), in Ca2+-sensing receptor (CaSR)-mediated extracellular Ca2+ influx and production of nitric oxide ( NO).METHODS: Human umbilical vein endothlial cells (HUVECs) were incubated with CaSR agonist spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels ( ROC) ] alone or combined with CaSR negative allosteric modulator Calhex 231+ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro 31-8220, or PKCα/β1 selective inhibitor Go 6976 (activate SOC, blocking ROC).The protein expression of STIM1 and Orai1 was determined by the method of immu-nofluorescence .The interaction between STIM 1 and Orai1 was examined by co-immunoprecipitation .The second to third passages of HUVECs were divided into STIM 1 and Orai1 short hairpin RNA group ( shSTIM1+shOrai1 group ) , vehicle-STIM1+vehicle-Orai1 group and control group , and then incubated with the 4 different treatments above .The intracellular Ca2+concentration ( [ Ca2+] I ) was detected using the fluorescent Ca 2+indicator Fura-2/AM.The production of NO was also determined by DAF-FM DA fluorescent probe .RESULTS:The protein expression of STIM 1 and Orai1 was located in the cytoplasm.Compared with control group , the localization of STIM1 and Orai1 in the cytoplasm was reduced after the HUVECs were incubated with Calhex 231+TPA, Ro 31-8220 or Go 6976, and the interaction of STIM1 and Orai1 was de-creased significantly .The [ Ca2+] I and the net NO fluorescence intensity in shSTIM 1+shOrai1 group were significantly re-duced after the 4 different treatments (P<0.05).CONCLUSION:STIM1 and Orai1 are components of SOC and ROC in store-and receptor-operated Ca 2+entry and NO generation .
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Intermediate-conductance Ca2+-activated K+channel ,also known as KCa3.1,IKCa and SK4,is widely distributed in fibroblasts,proliferating smooth muscle cells,endothelial cells,T lymphocytes,plasma cells,macrophages,and epithelial cells, and involved in the pathological and physiological processes such as vascular contraction,inflammation ,calcification,tissue fibrosis, immune response,malignant tumor,internal and external secretory glands. In recent years,it has been found that blocking the KCa3.1 pathway or knockouting the gene can significantly prevent the pathophysiological process of its involvement. The recent use of the specific blocker TRAM-34 in animals and humans shows its safety and tolerability,providing a new direction for the treatment of related diseases. In this article,the research progress in KCa3.1 related diseases in recent years is reviewed.
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Intermediate-conductance Ca2+-activated K+ channel, also known as KCa3.1, IKCa and SK4, is widely distributed in fibroblasts, proliferating smooth muscle cells, endothelial cells, T lymphocytes, plasma cells, macrophages, and epithelial cells, and involved in the pathological and physiological processes such as vascular contraction, inflammation, calcification, tissue fibrosis, immune response, malignant tumor, internal and external secretory glands. In recent years, it has been found that blocking the KCa3.1 pathway or knockouting the gene can significantly prevent the pathophysiological process of its involvement. The recent use of the specific blocker TRAM-34 in animals and humans shows its safety and tolerability, providing a new direction for the treatment of related diseases. In this article, the research progress in KCa3.1 related diseases in recent years is reviewed.
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Aim To investigate the effect of store-oper-ated calcium channel( SOCC) on autophagy in rat arte-rial smooth muscle cells A7 R5 . Methods Lentiviruses containing STIM1 or Orai1 gene were packaged in 293 T cells and then were used to infect rat arterial smooth muscle cells A7 R5 . The expression levels of STIM1 , Orai1 and Beclin 1 , a critical autophagy-regu-lating protein, of lentivirus-infected A7R5 cells, were detected by Western-blot. Autophagy in lentivirus-in-fected A7 R5 cells was induced by starvation or rapamy-cin, an inhibitor of mammalian target of rapamycin ( mTOR ) . Autophagy marker LC3 of these cells was detected by Western-blot. Results The constructions of vector pLV-STIM1 and pLV-Orai1 were confirmed by restriction enzymes digestion analysis. Compared with the control group, expressions of STIM1 or Orai1 protein was significantly increased after lentivirusLV-STIM1 and LV-Orai1infection, whereas the expressions of autophagy related protein Beclin-1 were down-regu-lated. Starvation or rapamycin stimulated A7R5 auto-phagy but overexpression of STIM1 or Orai1 significant-ly inhibited starvation or rapamycin induced autoph-agy. Conclusion Overexpression of store-operated calcium channel components STIM1 and/or Orai1 in rat arterial smooth muscle cells A7 R5 inhibit autoph-agy. This mechanism might contribute to the develop-ment of pulmonary arterial hypertension.
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Objective To study the effect of ganoderma lucidum polysaccharides on T cell subsets and AQP1, AQP3 expression of bladder cancer T24 cell line bearing mice.Methods 60 BALB/C nude mice were selection as experimental animals, bladder tumor bearing animal models were made by bladder cancer T24 cells subcutaneous injection, and were randomly divided into control group, cisplatin group, ganoderma lucidum polysaccharides and cisplatin group, cisplatin group given 25 mg/kgcisplatin intraperitoneal injection, cisplatin combined ganoderma lucidum polysaccharide group given 200 mg/kg ganoderma lucidum polysaccharide lavage, 25 mg/kg cisplatin intraperitoneal injection, the control group given quite a volume normal saline lavage.Then tumor volume and weight, peripheral blood T cell subsets and AQP1, AQP3, Caspase-3, Bax mRNA content in tumor tissue were determined.Results Cisplatin group, cisplatin combined ganoderma lucidum polysaccharide tumor volume and mass were significantly lower than the control group (P<0.05), cisplatin and ganoderma lucidum polysaccharide tumor volume and mass were significantly lower than that cisplatin group ( P<0.05 ); Cisplatin group, cisplatin combined ganoderma lucidum polysaccharides group CD4 + T cells, CD8 +T cells , CD4 +/CD8 + were significantly higher than that of control group (P<0.05), cisplatin combined ganoderma lucidum polysaccharide group CD4 +T cells, CD4 +/CD8 +were significantly higher than that of cisplatin group (P<0.05); Cisplatin group, cisplatin combined ganoderma lucidum polysaccharide group mices tumor tissues Bax, Caspase 3 mRNA content were significantly lower than the control group (P<0.05), cisplatin combined ganoderma lucidum polysaccharide group Bax,caspase 3 mRNA content were significantly lower than that of cisplatin group (P<0.05); Cisplatin group, cisplatin combined ganoderma lucidum polysaccharide group mice tumor tissue AQP1, AQP3 mRNA content were significantly lower than the control group (P<0.05); Cisplatin combined ganoderma lucidum polysaccharide group AQP1, AQP3 mRNA content were significantly lower than cisplatin group (P<0.05 ). Conclusion ganoderma lucidum polysaccharide can inhibit tumor growth and enhance cellular immune function of bladder cancer T24 cell line bearing mice, and adjust the expression of pro-apoptotic genes, AQP1 and AQP3.
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Objective To summarize the clinical,radiographic and genetic features of a family with metatropic dysplasia,in order to improve the level of understanding and diagnosis of this disease.Methods The proband,a one-year old boy,was diagnosed as metatropic dysplasia.His mother was 26 years old with mildly phenotype.Their clinical features and bone X-ray findings were analyzed.The DNA samples of the proband and his parents were collected.The coding exons and flanking introns regions of transient receptor potential vanilloid 4 (TRPV4) gene were amplified by polymerase chain reaction (PCR) and analyzed by DNA automatic detector.The pathology,diagnosis,treatment and prognosis were expounded.Results The symptoms of the boy were characterized by short extremities,a short trunk with progressive kyphoscoliosis,and craniofacial abnormalities that include a prominent forehead,midface hypoplasia,and a squared-off jaw.His motor development was slightly delayed.Mental development was normal.Bone X ray of the boy showed platyspondyly and severe metaphyseal enlargement with shortening of long bones and irregularities and delayed ossification of epiphysis.The patient and his mother were heterozygous for the nucleotide substitutions c.2396 ＞ T (p.P799L) in TRPV4 gene.Conclusions The patient and his mother with metatropic dysplasia were diagnosed with TRPV4 gene analysis.The patient showed typical clinical features.His mother was mild.Metatropic dysplasia had significantly clinical heterogeneity.Gene analysis is helpful for the diagnosis.
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[ ABSTRACT] AIM:To investigate the transient outward potassium channel protein expression in paraventricular nucleus (PVN) and its contribution to renal sympathetic nerve activity (RSNA) in rats with chronic heart failure (CHF). METHODS:A rat model of CHF was prepared by acute myocardial infarction that was induced by ligation of the left ante -rior descending coronary artery .Four weeks after heart failure , echocardiogram was applied to identify the CHF model and plasma norepinephrine (NE), serum NH2-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA. The expression of ransient outward potassium channel proteins Kv 4.2 and Kv4.3 at mRNA and protein levels was deter-mined by real-time PCR and Western blot .The mean arterial pressure ( MAP) , heart rate ( HR) and RSNA were measured in anesthetized rats with PVN microinjection of potassium channel blockers 4-AP.RESULTS:In CHF group , the rat car-diac function and Kv4.2 and Kv4.3 expression in PVN were obviously lower while plasma NE and serum NT-proBNP were obviously higher than those in sham group .Microinjection of 4-AP into PVN induced an increase in MAP , HR and RSNA in both sham and CHF rats , while the CHF rats exhibited smaller responses to 4-AP than sham-operated rats .CONCLU-SION:Downregulation of Kv4.2 and Kv4.3 expression in the PVN may be a potential mechanism for sympathoexciation in the rats with chronic heart failure .
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<p><b>OBJECTIVE</b>To explore the material basis of conduction along meridian.</p><p><b>METHODS</b>Sixty SD rats(30 males,30 females) were randomly assigned into a normal group,an acupuncture group,a verapamil blocking group and a 0.9%NaCl blocking group(control group),15 rats in each one. Fluo 3-AM(calcium fluorescence probe) was injected at the observation part in femoral stomach meridian of foot-(meridian part) and the approaching femoral meridian part(non-meridian part) in the normal group and the acupuncture group,and then incubation was applied. In the verapamil blocking group,verapamil was injected at local meridian part and non-meridian part,and in the control group 0.9%NaCl was injected. Then Fluo 3-AM was injected at the meridian part and non-meridian part in the two groups,and incubation was implemented. Caimaging changes in cells were recorded for more than 20 min after injection of every part in each group respectively. After the above operations in the last three groups,acupuncture was used at "Zusanli"(ST 36) immediately,with electroacupuncture for one min,then Caimaging changes in cells at the meridian and non-meridian parts were recorded for more than 20 min.</p><p><b>RESULTS</b>In the normal group, Cafluorescence intensity at the meridian part was higher than that at the non-meridian part. In the acupuncture group,after acupuncture Cafluorescence intensity at the meridian part was obviously higher than before,but the change before and after acupuncture was not apparent at the non-meridian part. After verapamil blocking local calcium channel and acupuncture,the Cafluorescence of the meridian part did not strengthen,and the change of that before and after acupuncture at the non-meridian part was not obvious. In the control group,after injecting 0.9%NaCl at local part,Cafluorescence intensities of the meridian and non-meridian parts showed no obvious change,so was that before and after acupuncture.</p><p><b>CONCLUSIONS</b>The voltage-gated calcium channel at the meridian part is highly correlated with its tissue cells exciting conduction.</p>
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Objective To investigate the role of AQP2 and Na +-K +-ATPase in the pathogenesis of kidney injury with multiple organ dysfunction syndrome,and try to find the express characteristics of them.Methods A total of 72 healthy rats were randomly (random number) divided into two groups:control group (n =24) and Lipopolysaccharide group (n =48).The Lipopolysaccharide group rats were injected with 5 mg/kg lipopolysaccharide at the beginning while the control group was 0.9％ sodium chloride.After the model was succeeded,the rats were put to death at 6 h,12 h,24 h,2 days,3 days and 5 days equally.The urine and blood were collected.Blood were used biochemical tests to check.kidney AQP2 protein and mRNA expression level in the organization were applied the immune organized and RT-PCR technique to detect.Applied kit for determining the content and activity of sodium/potassium-atpase.Results The volume of urine in LPS group decrease quickly at 12 h and 24 h,but increased after 2 days.Urea nitrogen and creatinine increased gradually,and peaked at 48 h,after then gradually decline.AQP2 mRNA and protein expression decreased,and minimize at 48 h.The content of Na+-K+-ATP ase has no obvious difference,but the activity significantly decreased at the beginning,then increased gradually,but it was still lower than the control group.Conclusions In renal injury rats model with multiple organ dysfunction syndrome,AQP2 is the structure of renal reabsorption function,while Na +-K +-ATPase directly involved in or indirectly reflected the state of kidney energy metabolism.Recovery of AQP2 protein and energy metabolism,before the rat kidney function improved.
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Pancreatic cancer is a kind of highly malignant aggressive cancers.Perinearal growth is one of the importcant biological characteristics of pancreatic cancer.Perineural invasion is an independent prognostic indicator of its prognosis.However,the mechanism has not yet completely clear.The pancreatic cancer perineural invasion mechanism research has been the focus of scholars to discuss,however it' s difficult to break through.Therefore,the discussion pancreatic violation of the peripancreatic neural mechanism for early clinical find,early treatment is essential.The mechanisms of pancreatic cancer research,from all kinds of adhesion molecule to the nerve growth factor,related ligand protein path to susceptibility gene expression,have been reported largely,which helps enhance people' s awareness of peripancreatic neural invasion.At the same time,perineural invasion in the early detection of disease,prolonging survival period and improving the quality of life has important significance.Now the progresses of reviews in recent years are discussed as follows.
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As one of the chronic diseases,asthma,plays a serious impact on human daily life.Asthma in children has showed an increasing trend in recent years,but the mechanisms of asthma are not yet clear.Studies have found that store-operated calcium entry(SOCE) plays an important role in the physiological activity of the body.The enhanced SOCE activity can promote cell growth,proliferation,and migration of a variety of cell types.SOCE important molecules STIM1 and ORAI1 may be involved in the asthmatic airway occurrence of hyperresponsiveness and airway remodeling,and closely to the asthmatic development.
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Objective To observe the physiopathologic changes of lung in rats with acute ischemic kidney injury,and to study the roles of cytokine,epithelial sodium channel protein (ENaC) and aquaporin 1 (AQP1) in acute lung injury brought on by acute ischemic kidney injury in rats.Methods A total of 60 healthy male Wistar rats (300-320 g) were randomly (random number) divided into control groups (group A,n =30) and acute kidney injury group (group B,n =30).The model of acute ischemic kidney injury in rats was made by bilateral renal arteiovenous blockage with clamps.Six rats of each group were sacrificed at 0,2,4,6 and 8 hours after modeling.Lung tissue of rats was harvested and stained with hematoxylin-eosin (HE) staining method,and the pathological changes of lung were observed under microscope.The ratio of wet and dry weight (W/D) of lung was calculated.The levels of protein in bronchoalveolar lavage fluid (BALF) were measured.The levels of IL-6 and TNF-α both in serum and BALF were tested.The concentrations of AQP1 and α-ENaC in lung were measured.Results At six hours after modeling,the pH value of arterial blood of rats in group B began to get lowered compared to group A.There was no difference in partial pressure of oxygen in arterial blood between two groups during entire period of experiment (P ＞0.05).Protein level in BALF and W/D of lung increased significantly two hours after modeling in rats of group B (P ＜ 0.05).The histopathological changes of acute lung injury including swollen aleolar epithelium,widened interalveolar septum,edema of alveoli and alveolar interstitium,alveolar neurophil sequestration,erythrocytes and protein in exudates were observed.The levels of TNF-α and IL-6 in serum and in BALF began to increase at two hours after modeling.The levels of AQP1 and α-ENaC of lung in rats with acute kidney injury decreased gradually and were lower than those in rats of group A (P ＜0.05).Conclusions Aleolar epithelial-endothelial barrier function was already compromised at the beginning of AKI,suggesting the acute lung injury was already brought on.The levels of TNF-α,IL-6 in serum and in BALF increased after the occurrence of acute kidney injury.The decreases in lung AQP1 and α-ENaC might contribute to the lung injury caused by early acute kidney injury.
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Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.
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Animais , Ratos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Trimetazidina/farmacologia , Vasodilatadores/farmacologia , Ácidos Graxos/sangue , Glucose/análise , Miócitos Cardíacos/metabolismo , Canais de Potássio/metabolismo , Ratos Sprague-Dawley , EstreptozocinaRESUMO
Recent several studies have shown that the genetic variation of SCN5A is related with atrioventricular conduction block (AVB); no study has yet been published in Koreans. Therefore, to determine the AVB-associated genetic variation in Korean patients, we investigated the genetic variation of SCN5A in Korean patients with AVB and compared with normal control subjects. We enrolled 113 patients with AVB and 80 normal controls with no cardiac symptoms. DNA was isolated from the peripheral blood, and all exons (exon 2-exon 28) except the untranslated region and exon-intron boundaries of the SCN5A gene were amplified by multiplex PCR and directly sequenced using an ABI PRISM 3100 Genetic Analyzer. When a variation was discovered in genomic DNA from AVB patients, we confirmed whether the same variation existed in the control genomic DNA. In the present study, a total of 7 genetic variations were detected in 113 AVB patients. Of the 7 variations, 5 (G87A-A29A, intervening sequence 9-3C>A, A1673G-H558R, G3578A-R1193Q, and T5457C-D1819D) have been reported in previous studies, and 2 (C48G-F16L and G3048A-T1016T) were novel variations that have not been reported. The 2 newly discovered variations were not found in the 80 normal controls. In addition, G298S, G514C, P1008S, G1406R, and D1595N, identified in other ethnic populations, were not detected in this study. We found 2 novel genetic variations in the SCN5A gene in Korean patients with AVB. However, further functional study might be needed.
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Humanos , Bloqueio Atrioventricular , DNA , Éxons , Variação Genética , Íntrons , Reação em Cadeia da Polimerase Multiplex , Regiões não TraduzidasRESUMO
Recent several studies have shown that the genetic variation of SCN5A is related with atrioventricular conduction block (AVB); no study has yet been published in Koreans. Therefore, to determine the AVB-associated genetic variation in Korean patients, we investigated the genetic variation of SCN5A in Korean patients with AVB and compared with normal control subjects. We enrolled 113 patients with AVB and 80 normal controls with no cardiac symptoms. DNA was isolated from the peripheral blood, and all exons (exon 2-exon 28) except the untranslated region and exon-intron boundaries of the SCN5A gene were amplified by multiplex PCR and directly sequenced using an ABI PRISM 3100 Genetic Analyzer. When a variation was discovered in genomic DNA from AVB patients, we confirmed whether the same variation existed in the control genomic DNA. In the present study, a total of 7 genetic variations were detected in 113 AVB patients. Of the 7 variations, 5 (G87A-A29A, intervening sequence 9-3C>A, A1673G-H558R, G3578A-R1193Q, and T5457C-D1819D) have been reported in previous studies, and 2 (C48G-F16L and G3048A-T1016T) were novel variations that have not been reported. The 2 newly discovered variations were not found in the 80 normal controls. In addition, G298S, G514C, P1008S, G1406R, and D1595N, identified in other ethnic populations, were not detected in this study. We found 2 novel genetic variations in the SCN5A gene in Korean patients with AVB. However, further functional study might be needed.
Assuntos
Humanos , Bloqueio Atrioventricular , DNA , Éxons , Variação Genética , Íntrons , Reação em Cadeia da Polimerase Multiplex , Regiões não TraduzidasRESUMO
Objective To study the influence of the Runzaoling on AQP1 and AQP5 in submaxillary gland of mice with Sjogren syndrome.Methods Sjogren syndrome mice models were setup by innducement method and divided into six groups randomly,including A group(blank group),B group(model group),C group (low dose group),D group(moderate dose group),E group(high dosage group)and F group(prednisone group).Immunohistochemical method was used to detect the of expressions of AQP1 and AQP5 of submaxillary gland in model mice.Result AQP1 expression showed:scattered flavescent particles were only found in submaxillary gland of group B and group C;AQP5 expression showed:brown-stained granules can be found in gland alveolous teleblem,lateral membrane,and basal lamina of submaxillary gland,secretory duct,and duct epithelia in B group mice;light brawn-stained granules can be found in group C mice;attenuated or disappear stained granules were found in acinus,secretory tube,and duct in D,E,and F group mice.Conclusion Runzaoling Can raise the expression of AQP5 in submaxillary gland of SS mice and increase the absorption quantity of water.