ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

Objective To investigate the effect and mechanism of Feixin Decoction(Astragali Radix,Pericae Semen,Carthami Flos,Descurainiae Semen Lepidii Semen,Paeoniae Radix Rubra,etc.)on monocrotaline-induced pulmonary arterial hypertension(PAH)rats based on peroxisome proliferator-activated receptor-γ/nuclear factor-κB(PPAR-γ/NF-κB)signaling pathway.Methods Forty-eight male SD rats were randomly divided into normal group,model group,Sildenafil group(0.025 g·kg-1)and low-,medium-and high-dose of Feixin Decoction groups(11.7,23.4,46.8 g·kg-1).PAH rat model was established by single intraperitoneal injection of monocrotaline solution(60 mg·kg-1).After 1 hour of modeling,the rats were given intragastric administration once a day for 28 days.Hemodynamic and echocardiographic parameters including right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI),pulmonary artery acceleration time(PAAT),pulmonary artery ejection time(PET),tricuspid annular plane systolic excursion(TAPSE),right ventricular internal diameter(RVIDd)and right ventricular anterior wall thickness(RVAWT)were measured in each group.The pathological changes of pulmonary arterioles were observed by HE staining.The expression level of α-smooth muscle actin(α-SMA)in rat pulmonary artery was detected by immunofluorescence.The levels of plasma interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The expression levels of PPAR-γ/NF-κB signaling pathway-related proteins were detected by immunohistochemistry and Western Blot.Results Compared with the normal group,the RVSP,mPAP,RVHI,RVIDd and RVAWT of the model group were significantly increased(P＜0.01).PAAT,PAAT/PET and TAPSE were significantly decreased(P＜0.01).The wall of pulmonary arterioles was significantly thickened,and the percentage of wall thickness of pulmonary arterioles to vascular diameter and the percentage of vascular wall area to total cross-sectional area of pulmonary arterioles were significantly increased(P＜0.01).The positive expression rate of α-SMA protein in pulmonary artery was significantly increased(P＜0.01).The levels of plasma IL-1β,IL-6 and TNF-α were significantly increased(P＜0.01).The positive expression rate of PPAR-γ protein in lung tissue was significantly decreased(P＜0.01),and the positive expression rate of NF-κB protein was significantly increased(P＜0.01).The protein expressions of PPAR-γ and IκB-α in lung tissue were significantly down-regulated(P＜0.01).The protein expression ratio of p-NF-κB/NF-κB was significantly increased(P＜0.01).Compared with the model group,RVSP,mPAP,RVHI,RVIDd and RVAWT in each administration group were significantly decreased(P＜0.05,P＜0.01),while PAAT,PAAT/PET and TAPSE were significantly increased(P＜0.05,P＜0.01).The thickness of the vascular wall was significantly reduced,and the percentage of the wall thickness of the pulmonary arterioles to the diameter of the blood vessels and the percentage of the vascular wall area to the total cross-sectional area of the small arteries were significantly reduced(P＜0.05,P＜0.01).The positive expression rate of α-SMA protein in pulmonary artery was significantly decreased(P＜0.05,P＜0.01).The plasma levels of IL-1β,IL-6 and TNF-α were significantly decreased(P＜0.05,P＜0.01).The positive expression rate of PPAR-γ protein in lung tissue was significantly increased(P＜0.05,P＜0.01),and the positive expression rate of NF-κB protein was significantly decreased(P＜0.05,P＜0.01).The protein expression of PPAR-γ in lung tissue was significantly up-regulated(P＜0.05,P＜0.01),and the protein expression ratio of p-NF-κB/NF-κB was significantly decreased(P＜0.01).The protein expression of IκB-α in the lung tissue of rats in the high-dose group of Feixin Decoction was significantly up-regulated(P＜0.01).Conclusion Feixin Decoction can improve pulmonary artery pressure,right ventricular dysfunction and pulmonary vascular remodeling in PAH rats induced by monocrotaline.The mechanism may be related to the regulation of PPAR-γ/NF-κB signaling pathway to inhibit inflammatory response.

Objective To monitor heart-related parameters of hypoxic pulmonary hypertension(PH)mouse models induced by hypoxia alone and hypoxia combined with vascular endothelial growth factor receptor inhibitor SU5416 using echocardiography,and to construct the prediction equation of right ventricular systolic pressure(RVSP).Twenty-four C57BL/6J male mice were randomly divided into simple hypoxia group(group A),hypoxia combined with SU5416 group(group B),control group(group C),each group 8 mice.Hypoxic PH models were constructed with hypoxia alone and hypoxia combined with SU5416 in group A and group B,respectively.Echocardiography was performed before and during modeling(2,3,4 weeks after interventions),and the relevant parameters were obtained.RVSP was measured using right heart catheterization after the last echocardiography.The changes of ultrasonic parameters were observed,the correlations of ultrasonic parameters 4 weeks after intervention with RVSP were observed,and linear equations for predicting RVSP were established.Results With time going,during modeling,pulmonary artery diameter(PAD),PAD/aorta diameter(AOD)and right ventricle anterior wall thickness(RVAWT)increased,while heart rate,pulmonary artery acceleration time(PAAT),PAAT/pulmonary artery ejection time(PAET)and tricuspid annular plane systolic excursion(TAPSE)decreased in group A and B(all P＜0.05).Three and 4 weeks after interventions,PAET,PAAT/PAET and TAPSE in group B decreased compared with those in group A(all P＜0.05).Four weeks after interventions,RVSP in group A and B were highly correlated with PAD/AOD,RVAWT,PAAT,PAAT/PAET and TAPSE(all P＜0.05).The linear regression equations of PAAT/PAET and TAPSE for predicting RVSP in simple hypoxic PH mice models included RVSP=-161.7 ×(PAAT/PAET)+63.85,as well as RVSP=-36.53 ×TAPSE+71.55,while of predicting RVSP in hypoxia combined with VEGFR-2 inhibitor PH mouse models were as follows:RVSP=-266.4 ×(PAAT/PAET)+91.59,RVSP=-69.14 × TAPSE+116.5.Conclusion Four weeks after inerventions,the phenotypes of hypoxic PH mouse models induced by hypoxia alone and hypoxia combined with SU5416 became obvious.Prediction equations of RVSP established based on PAAT/PAET and TAPSE obtained with echocardiography could provide references for relevant research.

Pulmonary hypertension(PH)is a progressive pulmonary vascular disease that can lead to right heart failure and death.In recent years,the incidence of PH has been increasing year by year and there is a lack of effective treatment.TCM can play an important synergistic role in the treatment of PH.Pulmonary vascular remodeling is a core pathological feature of PH,which is closely related to the physiological structure and pathological changes of the collaterals.Based on the collateral disease theory,this article described the key pathogenesis of PH in TCM and Western medicine,including the lesions of the pulmonary and cardiovascular complexes and pulmonary vascular remodeling,analyzed the physiology of the"collateral-vessel"in PH,sorting out the pathological correlation,and explored TCM targeting pulmonary vascular remodeling in the identification and treatment of PH,so as to provide a new way of thinking for the clinical treatment of PH.

Objective To explore the effect of electroacupuncture (EA) at tusanli (ST36) on regulation of stress response under different doses of etomidate anesthesia in rats.Methods Sixty male Sprague-Dawley rats, weighing 280-310 g, were randomly divided into control group (group C), model group (group M), etomidate 60 mg/kg group (group E1), etomidate 30 mg/kg group (group E2), etomidate 60 mg/kg combined with EA group (group EA1) and etomidate 30 mg/kg combined with EA group (group EA2), n=10 in each group.All groups received inferior caudal trunk transection at the level between sacral spinal nerve 3 and 4 (S3, S4) to prepare acute stress response model except group C.Group M received no others treatment.The rats in group E1, group EA1, group E2 and group EA2 were intraperitoneally injected with 60, 60, 30 and 30 mg/kg etomidate, respectively.Group EA1 and group EA2 received EA ST36.The points were stimulated at a frequency of 2/100 Hz with 1 mA output and a dilatational wave, which lasted for 30 min.ACTH and Cor levels were measured by ELISA.The c-fos protein expression in hypothalamic tissue was examined by Western blot.Results Compared with group C, ACTH and Cor levels, and hypothalamic expression of c-fos protein in group M were significantly increased (P<0.05).Compared with group M, serum ACTH and Cor levels, and hypothalamic expression of c-fos protein in groups E1, E2, EA1 and EA2 were significantly decreased (P<0.05).Compared with group E1, serum ACTH and Cor levels, and hypothalamic expression of c-fos protein were significantly higher in groups E2 and EA1 (P<0.05).Compared with group E2, serum ACTH level and hypothalamic expression of c-fos protein were significantly lower in group EA2 (P<0.05).Conclusion EA at ST36 regulating stress response under etomidate anesthesia in rats is effective and two-way, and the mechanism may be due to the release of neurotransmitters induced c-fos protein in hypothalamus.

Objective To compare three rat models of acute stress response and to explore an ideal experimental rat model for research of acute stress response .Methods A total of 40 clean grade male SD rats were randomly ( by random number ) divided into 4 groups ( n=10 each ):Normal group ( group I ) , caudal trunk transection group ( group II), burn group (group III), and amputation group (group IV).The group I received no special treatment , the group II received inferior caudal trunk transection at the level between sacral spinal nerve 3 and 4 (S3, S4), the group III was inflicted with 30%total body surface area ( TBSA) grade 3 burn on the back , and the group IV had an amputation of the left lower limb as severe traumatic stress .Rats in each group were killed at 30 minutes after treatment and blood samples were collected for measuring serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels by ELISA. The c-fos protein expression in hypothalamic tissue was examined by immunohistochemistry .Results Compared with the group I, serum ACTH and CORT levels , and hypothalamic expression of c-fos protein in the group II , III, IV were significantly increased ( P <0.05 ) .Compared with the group III , serum ACTH and CORT levels , and hypothalamic expression of c-fos protein were significantly higher in the group II and IV ( P <0.05 ) , while there was no significant difference between the group II and IV (P>0.05).Conclusions The preparation of acute stress response model induced by inferior caudal trunk transection has simple operation steps and produces a traumatic injury to a similar degree , and quite well reflects the acute stress response in humans caused by sudden accident .Therefore it is a quite good method to establish acute stress response and deserves further investigation .

Objective There is a lack objective methods for the diagnosis of postoperative cognitive dysfunction (POCD).This study aimed to investigate the influence of propofol or etomidate anes-thesia on the postoperative cognitive function and serum S 100βprotein level in infants . Methods This study included 100 hernia infants aged 1-3 years treated by laparoscopic herniorrhaphy under propofol (n=50) or etomidate anesthesia (n=50).At 1 day before and 3 days after surgery, we assessed the cognitive function of the patients using Bayley Scales of Infant and Toddler Development ( BSID-Ⅲ) and further divided each group into a POCD and a non-POCD sub-group based on the results of diagnosis made according to the Z-scores.Using ELISA, we measured the levels of the serum S100βpro-tein in the iliac venous blood drawn preoperatively ( T0 ) and before PACU ( T1 ) and compared them between the POCD and non-POCD groups. Results At 3 days after operation, POCD was observed in 10 cases (20.0%) in the propofol group and 9 cases (18.0%) in the etomidate group, with no statistically significant differences between the two (P>0.05).The level of the serum S100βprotein was markedly elevated in both the propofol and etomidate groups at T 1 as compared with that at T0(P<0.05), and so was it in the POCD in comparison with that in the non-POCD group (P<0.05), with no statistically significant differences between the two groups at T1(P>0.05).A significant correlation was found between the postoperative S 100βlevel and POCD at 3 days after surgery in both the propofol (r=0.842, P=0.001) and the etomidate group (r=0.821, P=0.001). Conclusion Propofol and etomidate anes-thesia can induce different degrees of postoperative decline of cognitive function in 1-3 years old infants .The post-anesthesia elevation of the serum S100βprotein level is positively correlated with early postoperative POCD and indicates various degrees of brain damage .

Objective To investigate the influence of electroacupuncture(EA) in different points combined with spinal anesthesia on acute stress response and mechanisms related with expression of spinal c-fos protein. Methods Fifty adult male Sprague-Dawley rats were randomly divided into 5 groups:groupⅠwere normal rats receiving only 50μL saline intrathecal IT injection;groupⅡwere docked rats receiving IT with 50 μL saline;groupⅢ were docked rats receiving IT injection of 50 μL, 2.5 μg fentanyl; group Ⅳwere docked rats receiving IT injection of fentanyl 50μL and EA at′zu-san-li′;groupⅤwere docked rats receiving EA at′er xue′and IT fentanyl. Serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were measured by ELISA. Determined the c-fos protein expression levels of L4-6 spinal by western blotting. Result GroupⅡACTH, CORT levels and c-fos expression was significantly higher than those in groupⅠ(P<0.01). Compared with groupⅡ, groupⅢ,ⅣandⅤhad higher ACTH and CORT levels (P<0.05). However, c-fos expression in the spinal cord between groupⅡandⅢshowed no difference (P>0.05). Between groupⅢandⅣ, no differences in serum hormone levels (P > 0.05) were detected. In group Ⅴ the c-fos expression was lower than that of the Ⅳ group (P < 0.01). Conclusion Body acupuncture and auricular electrical stimulation combined with intrathecal anesthesia were effective to reduce pain in rats with acute stress reactions. Under intrathecal anesthesia, auricular stimulation played a better role of non-nerve block region, and the mechanism may be due to the release of neurotransmitters induced c-fos protein in spinal cord.

Objective To investigate the relationship among the concentration of plasma interleukin (IL)-10 and plasma IL-13 and the clinical therapeutic effect in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods Thirty-six AECOPD inpatients were enrolled in this study.Blood samples of the subjects were collected as soon as hospitalization, and plasma IL-10 and IL-13concentrations were analyzed by enzyme-linked immunosorbent assay.The clinical manifestations of subjects were quantified by a special designed score standard, and were evaluated at the time points of hospitalization, 48 hours treatment and 96 hours treatment.The therapeutic effect was evaluated by clinical manifestations score combined with pulmonary ventilation functional parameter.Eventually, the correlation among the concentration of IL-10 concentration and IL-13 and the clinical therapeutic effect were analyzed.Results The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-10 concentration after 48 hours treatment were 0.85 and 0.48 respectively,then, 0.64 and 0.52 after 96 hours treatment.The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-13 concentration after 48hours treatment were -0.41 and -0.34, after 96 hours treatment , correlation coefficients between clinical manifestations score decrease with plasma IL-13 concentration was -0.36.All of the above correlation coefficients were statistically significant.Conclusion Plasma IL-10 concentration was positively, whereas, IL-13 concentration was negatively correlated with the therapeutic effect in AECOPD patients.

Objective To investigate the association of the expression level of anti-apoptosis protein p-AKT and gastric mucasal injury induced by indomethacin in mice.Methods The cytotoxicity induced by indomethacin was measured by LDH assay.The p-AKT expression levels were measured in the gastric mucosal tissues from C57BL/6 mice and rat gastric mucosal (RGM-1) cell lines treated with indomethacin lay western blotting.Results The cytotoxicity induced by indomethacin was in a dose dependent manner.Compared with the control,a typical histological appearance of gastric ulcer was observed in the gastric mucosa of in domethacin-administered mice;p-AKT protein expression in the gastric mucosa of mice and RGM-1 cell lines was decreased after treated with indomethacin.Conclusion The reduction of Anfi-apoptesis protein p-AKT expression may be a new mechanism for the gastric mucosal injury induced by indomethacin.