Effects of intranasal administration of glial cell line-derived neurotrophic factor on postoperative cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the effects of intranasal administration of glial cell line-derived neurotrophic factor (GDNF) on postoperative cognitive dysfunction in aged rats.Methods:Forty healthy Sprague-Dawley rats of both sexes, aged 21-23 months, weighing 480-600 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group S), operation group (group O), intranasal administration of low-dose GDNF group (group G1) and intranasal administration of high-dose GDNF group (group G2). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O, G1 and G2 groups, while the rats in group S only received sham operation.The rats in group G1 and group G2 were intranasally treated with GDNF 25 and 50 μg (in 25 μl of PBS), respectively, and PBS 25 μl was nasally administered in group S and group O every day for 3 consecutive days after operation or sham operation.Morris water maze test was performed on days 3-7 after surgery, and then the rats were sacrificed, and hippocampal tissues were removed for determination of the expression of GDNF, high mobility group box 1 (HMGB1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), activated caspase-3 and Bax (by Western blot). Results:Compared with group S, the escape latency was significantly prolonged on days 5-7 after operation, the number of crossing the platform was reduced, time spent in the target quadrant was shortened, expression of GDNF was down-regulated, and expression of IL-1β, TNF-α, HMGB1, activated caspase-3 and Bax in hippocampi was up-regulated in group O, and the number of crossing the platform was reduced, time spent in the target quadrant was shortened, and expression of IL-1β and TNF-α was up-regulated in G1 and G2 groups ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 5-7 after operation, the number of crossing the platform was increased, time spent in the target quadrant was prolonged, expression of GDNF was up-regulated, expression of TNF-α, HMGB1, activated caspase-3 and Bax in hippocampi was down-regulated in G1 and G2 groups, and IL-1β in hippocampi was down-regulated in group G1 ( P<0.05). Compared with group G1, the expression of TNF-α in hippocampi was down-regulated ( P<0.05), and no significant change was found in the other parameters mentioned above in group G2 ( P>0.05). Conclusions:Intranasal administration of GDNF can improve postoperative cognitive dysfunction, and the mechanism may be related to inhibiting neuroinflammatory responses and neuroapoptosis in aged rats.

Application of Shakubatrivalsartan in 5 cases of pediatric dilated cardiomyopathy: case report and literature review / 中华实用儿科临床杂志

Objective:To investigate the safety and therapeutic effect of Shakubatrivalsartan in the treatment of pediatric dilated cardiomyopathy.Methods:Clinical information, treatment and prognosis of 5 cases with dilated cardiomyopathy in the First Affiliated Hospital of Xinxiang Medical University from June 2018 to December 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:A total of 5 cases of children with dilated cardiomyopathy were analyzed, including 3 males and 2 females with age of 12-17 years.Their median left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVDd), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 37% (20%-41%), 61 mm (59-67 mm), and 13 250 ng/L (12 310-21 823 ng/L), respectively.The median conventional treatment time was 5 months (1-12 months), in which, the condition of heart failure gradually progressed, and the median LVEF, LVDd and NT-proBNP levels were reduced to 33% (19%-37%), 61 mm (60-74 mm), 13 144 ng/L (8 086-15 137 ng/L). After less than 3 months of follow-up following conventional treatment plus Shakubatrivalsartan, NT-proBNP level significantly decreased in 5 cases.Besides, 4 cases had improved cardiac function, and the other one′s improvement was not obvious.The blood pressure of 5 cases decreased at varying degrees after medication of Shakubatrivalsartan, which should be closely monitored during drug titration.No adverse reactions were reported.Conclusions:Shakubatrivalsartan for the treatment of pediatric dilated cardiomyopathy is safe and effective, which can alleviate or reverse the process of myocardial remodeling and improve cardiac ejection fraction, thus improving the prognosis.

Effect of DA-JC4 on postoperative neuroinflammatory responses in aged rats / 中华麻醉学杂志

Objective:To evaluate the effect of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist DA-JC4 on postoperative neuroinflammatory responses in aged rats.Methods:Forty-five Sprague-Dawley rats, aged 21-23 months, weighing 530-630 g, provided by the Animal Experiment Center of Medical School of Zhengzhou University, were assigned into 3 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O) and DA-JC4 group (group G). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O and G groups.In group G, DA-JC4 10 nmol/kg (dissolved in 1 ml of sterile normal saline) was intraperitoneally injected immediately after the end of operation and at 24 and 48 h after operation.Western blot was used to determine the expression of hippocampal Bax, Bcl-2, activated caspase-3, Beclin-1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), high-mobility group box 1 protein (HMGB1), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) on day 3 after surgery.The Morris water maze test was performed on days 14-18 after operation to assess the cognitive function. Results:Compared with group S, the escape latency was significantly prolonged on days 15-18 after operation in group O and on day 18 after operation in group G, and the number of crossing the original platform was reduced, the time spent in the target quadrant was shortened, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was up-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was down-regulated in O and G groups ( P<0.05). Compared with group O, the escape latency was significantly shortened, and the number of crossing the original platform was increased, the time spent in the target quadrant was prolonged, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was down-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was up-regulated in group G ( P<0.05). Conclusion:The mechanism by which DA-JC4 reduces postoperative cognitive dysfunction may be related to inhibiting neuroinflammatory responses in aged rats.

Effect of exercise training on heat shock protein 70 expression during endotoxin-induced acute lung / 中华麻醉学杂志

Objective To evaluate the effect of exercise training on heat shock protein 70 (HSP70) expression during endotoxin-induced acute lung injury (ALI) in rats.Methods Thirty-two SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 175-220 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),group ALI,low-intensity exercise training group (group ET1) and high-intensity exercise training group (group ET2).The rats in ET1 and ET2 groups received 2-and 4-week treadmill exercise training before establishing the ALI model,while the rats in C and ALI groups received no training.ALI was induced by intravenously injecting 5 mg/kg lipopolysaccharide via the tail vein in ALI,ET1 and ET2 groups,and the equal volume of normal saline was given instead in group C.The animals were sacrificed,and the lungs were harvested for microscopic examination of the pathological changes of lung tissues which were also scored and for determination of wet to dry weight ratio (W/D ratio),concentrations of total protein,interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluid (BALF),and expression of HSP70 and nuclear factor kappa B (NF-κB) in lung tissues by Western blot.Results Compared with group C,the W/D ratio and pathological changes of lung tissues were significantly increased,the concentrations of total protein,IL-1 β and TNF-α in BALF were increased,the expression of NF-κB was up-regulated (P＜0.05),and no significant change was found in HSP70 expression in group ALI(P＞0.05).Compared with group ALI,the W/D ratio and pathological changes of lung tissues were significantly decreased,the concentrations of total protein,IL-1β and TNF-α in BALF were decreased,the expression of HSP70 was up-regulated,and the expression of NF-κB was down-regulated in ET1 and ET2 groups (P＜0.05).Conclusion Exercise training can attenuate the endotoxin-induced ALI through relieving the inflammatory responses,which may be related to up-regulating HSP70 expression in the lung of rats.

Molecular mechanism of Nifedipine inducing liver injury in children / 中华实用儿科临床杂志

Objective To establish the Nifedipine-induced liver cell damage model,and to investigate the cellular or molecular mechanism for children's liver cell damage.Methods The HepG2 cells were utilized to establish liver cell damage models.The optimal concentration and the optimal pretreatment time of Nifedipine-induced liver cell injury were confirmed.Western blot and real-time PCR(RT-PCR)were used to check the alteration in proteins and mRNAs level of the liver function-associated classic markers,which contained alkaline phosphatase(ALP),aspartate amino transferase(AST),glutamyl transpeptidase(γ-GT)and alanine aminotransferase(ALT).Additionally,flow cytometry(FCM),colony formation assay(CFA)and cell wound healing assay(CWHA)were utilized to check the effect of Nifedipine on the cell cycle progression and proliferation of HepG2.Results (1)The optimal concentration of Nifedipine was 20 mg/L and the optimal treatment period was 21 days for liver damage.(2)Western blot:intracellular ALT protein content after Nifedipine group was less than that of control group,while the protein levels of AST,γ-GT and ALP in the culture medium after Nifedipine addition(3.55 ± 0.05,4.91 ± 0.055,3.51 ± 0.05,3.08 ± 0.08) were higher than those of control group(0.96 ± 0.02,1.03 ± 0.02,1.00 ± 0.05,0.90 ± 0.13),and the differences were all significant(t = -85.695,-117.582,-47.371,-33.260,all P<0.05).(3)The findings of RT-PCR showed that the mRNA levels of intracellular ALT,γ-GT and ALP in Nifedipine group(0.26 ± 0.02,0.05 ± 0.04, 0.05 ± 0.02)were lower than those of control group(1.13 ± 0.21,0.94 ± 0.10,1.03 ± 0.06),and the differences were all significant(t=7.233,127.436,25.687,all P<0.05).However,the mRNAs levels in purified culture me-dium in Nifedipine group(5.95 ± 0.05,3.13 ± 0.10,3.32 ± 0.08)were higher than those in control group(1.01 ± 0.08,1.00 ± 0.05,1.00 ± 0.05),and the differences were all significant(t= -92.339,-31.250,-43.007,all P<0.05).(4)The portion of G0/G1 phase in Nifedipine group[(84.09 ± 0.43)%]was more than that of control group[(30.93 ± 0.32)%],which had statistical significance(t=173.084,P=0.000).(5)In contrast with control group,the colony formation of cells in Nifedipine group declined from(97.10 ± 1.17)% to(38.56 ± 1.51)%(t=92.088,P=0.000)and the migration rate of cells wound healing was(56.37 ± 2.06)%,(25.00 ± 1.71)% sepa-rately(t=20.285,P=0.000).Conclusion Nifedipine may promote children's liver injury through regulating cell cycle related proteins.

Role of Nrf2/HO-1 signaling pathway in remote ischemic preconditioning-induced reduction of lipopolysaccharide-induced acute lung injury in mice / 中华麻醉学杂志

Objective To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in remote ischemic preconditioning-induced reduction of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods Sixty-eight healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-26 g,were divided into 4 groups (n =17 each) using a random number table:control group (group C),ALI group,remote ischemic preconditioning group (group RIPC) and brusatol plus remote ischemic preconditioning group (group B+RIPC).Normal saline 100 μl was intratracheally instilled in group C.ALI was induced by intratracheal instillation of LPS 5 mg/kg in group ALI.Mice in group RIPC were subjected to 6 cycles of 5-min ischemia followed by 5-min reperfusion in the right hindlimbs using a tourniquet,and 1 h later the model of ALI was established.Nrf2 inhibitor brusatol 2 mg/kg (in 100 μl of 1％ dimethyl sulfoxide) was intraperitoneally injected every other day for 10 days prior to establishment of the ALI model in group B.Brusatol 2 mg/kg was intraperitoneally injected every other day for 10 days prior to establishment of the ALI model,and remote ischemic preconditioning was performed at 1 h before establishment of the ALI model in group B+RIPC.Seven mice in each group were selected at 24 h after establishment of the ALI model,and bronchoalveolar lavage fluid (BALF) was collected for determination of protein concentrations and neutrophil count.Mice were then sacrificed and lungs were removed for determination of lung water content,myeloperoxidase (MPO) activity,contents of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α),and expression of Nrf2,HO-1 and high-mobility group box 1 protein (HMGB1) in lung tissues (by Western blot) and for examination of pathological changes (with a light microscope).Results Compared with group C,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly increased,and the expression of Nrf2,HO-1 and HMGB1 was up-regulated in group ALI (P＜ 0.05).Compared with group ALI,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly decreased,the expression of Nrf2 and HO-1 was up-regulated,and the expression of HMGB1 was down-regulated (P＜0.05),and the pathological changes were significantly attenuated in group RIPC.Compared with group RIPC,the lung water content,MPO activity,contents of IL-1β and TNF-α,and neutrophil count and protein concentrations in BALF were significantly increased,the expression of Nrf2 and HO-1 was down-regulated,and the expression of HMGB1 was up-regulated (P＜0.05),and the pathological changes were aggravated in group B+RIPC.Conclusion The activation of Nrf2/HO-1 signaling pathway is involved in remote ischemic preconditioning-induced reduction of LPS-induced ALI in mice.

Relationship between α7nAChR signaling pathway and regulatory T cells during vagus nerve stimulation-induced reduction of endotoxin-caused acute lung injury in mice / 中华麻醉学杂志

Objective To evaluate the relationship between α7 nicotinic acetylcholine receptor (α7nAChR) signaling pathway and regulatory T cells (Tregs) during vagus nerve stimulation-induced reduction of endotoxin-caused acute lung injury (ALI) in mice.Methods Clean-grade healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-25 g,were divided into 5 groups (n=10 each) using a random number table method:control group (group C),group ALI,vagus nerve stimulation group (group VNS),α-BGT group (group α-BGT) and vagus nerve stimulation plus α-BGT group (group VNS + α-BGT).After successful establishment of the model,the vagus nerve was stimulated for 30 s with a stimulus intensity of 0.5 mA,frequency of 20 Hz,an interval of 5 min,60 min in total.Sterile normal saline 100 μl was injected into the trachea,and the vagus nerve was only exposed but not stimulated in group C.In group ALI,the ALI model was established,and the vagus nerve was isolated but not stimulated.In group α-BGT,α-BGT 1 μg/kg was intraperitoneally injected,the ALI model was established 1 h later,and the vagus nerve was isolated but not stimulated.In group VNS+α-BGT,α-BGT 1 μg/kg was intraperitoneally injected,the ALI model was established 1 h later,and the vagus nerve was stimulated at 1 h after the end of establishment.Animals were sacrificed at 72 h after establishing the model,and lungs were removed for determination of lung water content,percentage of Tregs (using flow cytometry),myeloperoxidase (MPO) activity (by colorimetric assay),expression of α7nAChR (by Western blot) and contents of interleukin-10 (IL-10),transforming growth factor-β (TGF-β) and IL-1β (by enzyme-linked immunosorbent assay).Results Compared with group C,the lung water content,MPO activity and IL-1β content were significantly increased in the other four groups,the expression of α7nAChR was significantly down-regulated in ALI,α-BGT and VNS+α-BGT groups,the percentage of Tregs was significantly increased in group VNS,the IL-10 content was significantly decreased in ALI and α-BGT groups and increased in VNS and VNS+α-BGT groups,and TGF-β contents were significantly decreased in ALI,α-BGT and VNS+α-BGT groups and increased in group VNS (P＜0.05).Compared with group ALI,the lung water content,MPO activity and IL-1β content were significantly decreased,the expression of α7nAChR was up-regulated,and the percentage of Tregs and contents of IL-10 and TGF-β were increased in group VNS,and the TGF-β content in group α-BGT and contents of IL-10 and TGF-β in group VNS+α-BGT were significantly increased (P＜0.05).Compared with group VNS,the lung water content,MPO activity and IL-1β content were significantly increased,the expression of α7nAChR was down-regulated,and the percentage of Tregs and contents of IL-10 and TGF-β were decreased in α-BGT and VNS+α-BGT groups (P＜0.05).The contents of IL-1O and TGF-β were significantly higher in group VNS+α-BGT than in group α-BGT (P＜0.05).Conclusion Vagus nerve stimulation can activate α7nAChR signaling pathway and raise the percentage of Tregs,thus reducing ALI in mice.

Role of TRPM7 in sevoflurane preconditioning for inhibiting hippocampal neurons apoptosis and inflammatory responses induced by oxygen-glucose deprivation in rat / 重庆医学

Objective To investigate the role of transient receptor potential melastatin 7(TRPM7) in sevoflurane preconditioning for inhibiting hippocampal neurons apoptosis and inflammation response induced by oxygen-glucose deprivation(OGD).Methods Fifty SD rats of postnatal 1 d were selected for extracting hippocampal neurons and randomly divided into 5 groups,including the control group(C),sevoflurane preconditioning group (Sev),OGD group,Sev preconditioningt OGD group (Sev + OGD) and Sev preconditioning+ bradykinin+OGD group(combined group).After 1.5 h oxygen-glucose deprivation,reintroduction was performed,and then the normal culture was performed again for preparing the OGD model.Hippocampal neurons in the control group were normally cultured only;which in the Sev group conducted 2 ％ Sev preconditioning for 1 h;which in the OGD group only prepared the OGD model;which in the SEv+OGD conducted 2％ Sev preconditioning for 1 h,and prepared the OGD model after 24 h;which in the combined group was simultaneously added with bradykinin(final concentration 200μmol/L) in Sev preconditioning,other treatment was same to that in the Sev+OGD group.After 24 h normal culture,the mRNA and protein levels of TRPM7,apoptosis rate,survival rate,mRNA and supernatant protein levels of IL-1β and TNF-α of the hippocampal neurons were detected.Results Compared with the control group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,mRNA and supernatant protein levels of IL-1β and TNF-α in the OGD group were significantly increased(P＜0.05),whereas the survival rate was significantly decreased (P ＜ 0.05).Compared with the OGD group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,mRNA and supernatant protein levels of IL-1β and TNF-α in the Sev group were significantly decreased(P＜0.05),whereas the survival rate was significantly increased(P＜0.05).Compared with the Sev group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,the mRNA and supernatant protein levels of IL-1β and TNF-α in the combined group were significantly increased(P＜0.05),whereas the survival rate was significantly decreased(P＜0.05).Conclusion Sev preconditioning can attenuate hippocampal neurons apoptosis and inflammatory response after OGD via alleviating the overexpression of TRPM7.

Effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure / 中华实用儿科临床杂志

Objective To observe the effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure.Methods Thirty-six male New Zealand big-eared immature rabbits were randomly divided into 3 groups:Adriamycin(ADR) ± Simvastatin group(ADR-s group,n =12),in which ADR(1.5 mg/kg) received injection via the auricular vein of rabbits weekly,and the rabbits received oral Simvastatin [1.5 mg/(kg · d)] simultaneously for 12 weeks;ADR group (n =12),in which the rabbits received ADR like ADR-S group,and 9 g/L saline instead of Simvastatin;control group (CON group,n =12),which received the same amount of 9 g/L saline.Echocardiography examination was performed in 13th week.Myocardial fibrosis degree was detected by using MASSON staining,and the myocardial apoptosis was detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling.Colorimetric method was used to detect the myocardial concentration superoxide dismutase (SOD) and malondialdehyde (MDA).Enzyme-linked immunosorbent assay was used to detect serum B-type brain natriuretic peptide (BNP) level.Results (1) In CON group,the immature rabbits were all alive.Four rabbits died in ADR group,and the survival rate was 66.7％,while 2 rabbits died in ADR-s group,and the survival rate was 83.3％.(2)Compared with CON group,the left ventricular end diastolic diameter (LVEDd) and left ventricular end systolic diameter (LVESd) in ADR-s group and ADR group increased [(11.90 ±1.09) mm,(ll.34 ±0.92) mm vs.(10.73 ±0.48) mm;(9.80 ±0.88) mm,(8.47 ± 1.23) mm vs.(7.31 ±0.36) mm];left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) decreased [(17.65 ± 1.70)％,(22.58 ± 2.19)％ vs.(31.79 ± 2.58) ％;(41.35 ± 3.19) ％,(49.17 ± 3.53) ％ vs.(64.34 ± 3.97) ％],and all the differences were significant(all P ＜ 0.05);LVEDd and LVESd in ADR-s group were lower than those of ADR group,while LVEF and LVFS in ADR-s group were higher than those of ADR group,and the differences were significant(all P ＜ 0.05).(3)MASSON staining:compared with ADR group,there was less myocardial cell hyperplasia of fibrous tissue in ADR-s group.(4) Compared with CON group,the apoptosis index was higher in ADR and ADR-s group [(34.25 ±11.13) ％,(24.00 ±6.85)％ vs.(16.58 ± 5.34)％],but ADR-s group had less than ADR group,and the differences were significant (all P ＜ 0.05).(5) Compared with ADR group,SOD activity of ADR-s group was higher [(13.40 ± 2.68) kU/L vs.(10.66 ± 2.99) kU/L],but MDA content was lower [(5.67 ± 1.36) μmol/mg vs.(7.08 ±0.98) μmol/mg],and the differences were significant (all P ＜0.05).(6) Serum BNP level in ADR group and ADR-s group was higher than that of the CON group[(33.28 ±9.58) μg/L,(26.71 ±6.72) μg/L vs.(13.56 ±2.82) μg/L],while was higher in ADR group than that of ADR-s group,and the differences were significant (all P ＜ 0.05).Conclusions Simvastatin can protect cardiac function of immature rabbits with chronic heart failure.The possible mechanism may be the up-regulation of myocardial SOD activity,reduction of cell lipid peroxidation and inhibition of myocardial apoptosis.

Effect of neuregulin-1βcombined with captopril on myocardial cell apop-tosis and related gene expression in rats with chronic heart failure / 中国病理生理杂志

AIM:To study the effect of neuregulin-1 ( NRG-1β) or captopril alone and their combination on myocardial cell apoptosis and related gene expression in rats with chronic heart failure .METHODS:Young male Sprague-Dawley rats were randomly divided into sham-operated group, heart failure group, NRG-1βgroup, captopril group and combined treatment group .The volume overloaded heart failure model in the rats was established by aortocaval fistula .The cardiac function was evaluated by determining the changes of hemodynamics and plasma BNP level .The apoptotic index ( AI) of myocardial cells was assayed by TUNEL .The protein levels of p-Akt, Bax and Bcl-2 in left ventricular tissue were detected by Western blot .RESULTS: The LVEDP, AI and the expression of Bax were significantly lower in NRG-1βgroup, captopril group and combined treatment group than those in heart failure group ( P<0.05 ) , while the values of ±dp/dtmax and the protein levels of p-Akt and Bcl-2 were significantly higher in NRG-1βgroup, captopril group and com-bined treatment group than those in heart failure group (P<0.05).The effect of combined treatment group was more signifi-cant ( P<0.05) than that in NRG-1βgroup and captopril group .CONCLUSION: Neuregulin-1βor captopril alone and the combination of them effectively improve the cardiac function and inhibit myocardial cell apoptosis in chronic heart failure rats.The therapeutic effect of combination of NRG-1βand captopril is better than that of NRG-1βor captopril alone .

Effect of Simvastatin on expressions of myocardial chromogranin A and apoptosis signal-regulating kinase 1 of immature rabbits with chronic heart failure / 中华实用儿科临床杂志

Objective To observe the influence of Simvastatin on immature rabbit model of chronic heart failure(CHF),and to explore the possible protective mechanism of Simvastatin for the rabbits with CHF.Methods Thirty immature male rabbits were divided into 3 groups randomly:control group,heart failure group (HF group)and Simvastatin group(SIM group),10 rabbits in each group.The models of CHF were established by injecting Adrinmycin via the auricular vein of rabbits (1.5 mg/kg,once 1 week,for 12 weeks).The control group were injected the same amount of 9 g/L saline.SIM group were given both injection of Adrinmycin and Simvastatin [1.5 mg/(kg · d)for 12 weeks].The immature rabbit's cardiac function and myocardial morphology changes were evaluated.The expressions of chromogranin A (CgA) and apoptosis signal-regulating kinase 1 (ASK1) were evaluated.Results (1) In control group,the immature rabbits were all alive;in the other 2 groups,most immature rabbits were depressed and sluggish.The survival rate of HF group was 60％,while in SIM group the survival rate was 80％.(2)Compared with the control group,the left ventricular ejection fraction in HF group and SIM group decreased significantly [(40.05 ± 6.74)％,(50.18 ± 5.73) ％ vs.(65.93 ± 5.65) ％,all P ＜ 0.01],while in SIM group was higher than that of HF group,and the difference was significant (P ＜ 0.05);compared with HF group,the left ventricular end diastolic diameter and left ventricular end systolic diameter decreased in SIM group [(13.48 ± 1.24) mm vs.(16.23 ± 2.82) mm;(9.87 ± 0.85) mm vs.(11.13 ± 1.21) mm],and the differences were significant (all P ＜ 0.05).(3) Compared with the control group,the expression of CgA (mean optical density 142.24 ± 17.14,127.93 ± 12.12 vs.78.65 ± 6.78,P ＜ 0.05;integrated optical density 1 422.41 ± 167.34,1 279.37 ± 118.15 vs.786.54 ± 75.84,P ＜ 0.05) and ASK1 (mean optical density 140.32 ± 18.65,115.48 ± 12.30 vs.69.85 ± 6.54,P ＜ 0.05;integrated optical density 1 403.23 ± 165.67,1 158.79 ± 137.81 vs.698.58 ± 64.51,P ＜ 0.05) increased in the HF group and SIM group.While the expression in the SIM group decreased significantly compared with that of the HF group,and the difference was significant (P ＜ 0.05).Conclusions Simvastatin can improve cardiac function of immature rabbits with CHF.The mechanism of SIM may depress the expressions of CgA and ASK1.

Effects of intrathecal administration of dexmedetomidine on morphine tolerance and inflammatory response in rats / 重庆医学

Objective To investigate the effects of intrathecal dexmedetomidine administration on the development of morphine tolerance and spinal inflammatory responses.Methods Thirty-three male SD rats weighing 180～200 g were randomly divided into 3 groups (n=11):Saline group (group NS),Morphine group (group M) and Dexmedetomidine group (group Dex).Animals of group NS were intrathecally injected with 10 tμL of saline daily for seven days;Animals in group M were intrathecally injected with 15 μg of morphine daily for seven days;Animals in group Dex were intrathecally injected with a mixture of 15μg morphine and 1.5 μg dexmedetomidine daily for seven days.At 1,3,5 and 7 day of intrathecal injection,hot water tail-flick test were used to evaluate analgesic response to thermal stimuli.After the last episode of behavioral test,Western blot analysis was applied to determine the protein levels of Iba-1 (microglial marker),IL-1β,TNF-a and phospho-p38MAPK (p-p38) in the spinal cord.In addition,microglia in the spinal cord was immuno-stained with anti-Iba-1 antibody and the densities of microglia were calculated.Results In group M and Dex,the values of maximal possible effect (MPE) in tail-flick test decreased gradually along with repeated morphine administration (P＜0.05).Compared with group NS,the values of MPE in tail-flick test at 1,3,5 and 7 day of morphine tolerance were higher in group M (P＜0.05).Compared with group M,the values of MPE in tail-flick test at 3,5 and 7 day of morphine tolerance were higher in group Dex (P＜0.05).Compared with group NS,the spinal protein levels of Iba-1,IL-1L TNF-α and p-p38 as well as the density of Iba-1 positive cells in group M were increased (P＜0.05).However,Compared with group M,the of Iba-1,IL-1β,TNF-α and p-p38 as well as the density of Iba-1 positive cells were decreased(P＜0.05).Conclusion Intrathecal dexmedetomidine administration can attenuate morphine tolerance by inhibiting microglia-mediated inflammatory responses in the spinal cord.

Association between the polymorphism of interleukin-12B gene and coronary heart disease / 西安交通大学学报(医学版)

Objective To study the relationship between the polymorphism of interleukin-12B (IL-12B)gene and coronary heart disease.Methods We recruited 256 patients with coronary heart disease admitted to our department as the study group and 256 normal subjects as the control group.The polymorphism of IL-12B gene was detected by polymerase chain reaction and single nucleotide polymorphism.Coronary artery stenosis,visfatin,high sensitive C reactive protein and cardiac function were determined.Results The difference in rs15677380 and rs14050311 allele frequencies between the study group and the control group was significant (χ2 =6.19,7.24,P=0.045,0.021).The G allele of rs15677380 and C allele of rs14050311 were risk factors for coronary heart disease (OR=1.32,1.49).Conclusion IL-12B gene is associated with the occurrence and development of carotid atherosclerosis and participates in the development of coronary heart disease.

Effects of potassium aspartate and magnesium on ventricular arrhythmia in ischemia-reperfusion rabbit heart / 华中科技大学学报（医学）（英德文版）

The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischemia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome / 华中科技大学学报（医学）（英德文版）

Intracellular Ca2+ and Ca2+-dependent signaling molecule play an essential role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential (MAP) recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode's solution. Bradycardia was induced by com-plete ablation of atrioventrtcular node. A catheter was introduced into the right ventricle to pace at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2 μol/L) prolonged QT in-terval and ventricular MAP duration (MAPD), and increased transmural dispersion of repolarization (TDR) in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil (0.01-0.05 μmol/L) used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syn- drome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Insulin sensitivity and the diffuseness of coronary artery disease in humans / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study the relationship between insulin sensitivity and diffuse coronary artery disease.</p><p><b>METHODS</b>Ninety-two consecutive patients underwent coronary angiography were enrolled in the study. Relationships between the results of angiograms and both glucose tolerance and blood lipids were analyzed.</p><p><b>RESULTS</b>The mean age of the 92 patients (70 males, 22 females) was 65.4 +/- 6.3 y. In the 78 patients diagnosed by angiography as coronary artery disease, diffuse lesion was more common in diabetic patients than in those without a diabetes history (12/13 vs 24/65, P = 0.00026). Fasting glucose [(6.06 +/- 2.43) x 10(-3) mol/L vs (4.80 +/- 1.47) x 10(-3) mol/L, P = 0.009], glucose levels at one hour [(12.37 +/- 4.38) x 10(-3) mol/L vs (9.10 +/- 3.97) x 10(-3) mol/L, P = 0.001], two hours [(11.12 +/- 5.64) x 10(-3) mol/L vs (7.49 +/- 4.29) x 10(-3) mol/L, P = 0.003] and three hours [(8.11 +/- 5.51) x 10(-3) mol/L vs (5.56 +/- 3.46) x 10(-3) mol/L, P = 0.020] after food were higher in patients with diffuse coronary disease than in those with non-diffuse coronary disease. Differences in the insulin sensitivity index (ISI) between the two groups was statistically significant (-4.36 +/- 0.52 vs -3.89 +/- 0.69, P = 0.003). The incidence of multiple-vessel disease in diabetic patients was higher than that in non-diabetic patients (12/13 vs 33/65, P = 0.00565). Glucose levels at two hours [(10.22 +/- 5.57) x 10(-3) mol/L vs (7.67 +/- 4.43) x 10(-3) mol/L, P = 0.034] and three hours [(7.90 +/- 5.47) x 10(-3) mol/L vs (5.22 +/- 2.79) x 10(-3) mol/L, P = 0.007] after food were higher in patients with multiple-vessel disease than in those with single-vessel disease. Impaired insulin sensitivity without a history of diabetes mellitus was commonly seen in patients with coronary artery disease.</p><p><b>CONCLUSIONS</b>The diffuseness of coronary artery disease is associated with insulin sensitivity and blood glucose levels. Insulin resistance is a common phenomenon in non-diabetic patients.</p>