摘要:目的: 研究蛻皮甾酮對非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)表達的影響，并探索其可能的作用機制。 方法 :健康成年SD大鼠36只,隨機分為正常對照組12只與實驗組24只;正常對照組喂以普通基礎飼料,實驗組應用高脂飼料喂養。實驗12周末時將造模成功的實驗組大鼠隨機分為模型組與蛻皮甾酮治療組2個亞組,每組12只;正常對照組喂以普通基礎飼料至16周,模型組繼續應用改良高脂飼料喂養至16周,蛻皮甾酮治療組大鼠在高脂飲食同時加用蛻皮甾酮灌胃。實驗16周末時處死3組所有大鼠;檢測肝臟指數,血清與肝組織生化指標及肝組織病理改變;ELISA法檢測肝臟TNFα水平;免疫組化檢測各組大鼠肝組織中核因子κB蛋白表達情況。 結果 :蛻皮甾酮治療組血清膽固醇(TC)、丙氨酸氨基轉移酶(ALT)和天門冬氨酸氨基轉移酶(AST)明顯低于模型組(212±058比263±024,Plt;005;5336±1848比8460±3627,P＜005;14020±3595比24359±3638,P＜001);蛻皮甾酮治療組與模型組相比肝組織丙二醛(MDA)水平降低明顯(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P＜001),肝臟指數顯著降低(435±037比504±046,P＜001)，肝組織脂肪變性程度和炎癥活動度明顯減輕(546±037比630±049,P＜001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 結論 :蛻皮甾酮具有改善高脂飲食誘發的非酒精性脂肪性肝病大鼠肝臟酶學功能,通過增加肝組織SOD的含量和減少MDA的含量來減輕肝組織氧化應激水平,減輕肝組織TNFα和核因子κB來減輕肝臟炎癥,發揮防治非酒精性脂肪性肝病的作用。Abstract: Objective: To investigate the effect and possible mechanism of ecdysterone on the expression of tumor necrosis factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th week, the rats in the normal control group and model group were lavaged with normal sodium, and the rats in the ecdysterone group were lavaged with ecdysterone at 10 mg·kg-1·d-1. At the end of the 16th week, all rats were weighed, narcotized, sacrificed, and the liver index, biochemical indicators in serum and liver tissues and the hepatic pathological changes were observed. The expression of TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P＜005; 14020±3595 vs 24359±3638, P＜001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P＜001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P＜001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P＜001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P＜001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P＜001) in ecdysterone group compared with model group. Conclusion : The effects of ecdysterone in preventing NAFLD in rats could be related to the increase of SOD content in hepatic tissue and the decrease of MDA content, tumor necrosis factorα and NFκB.
ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
ObjectiveTo explore the relationship between morning symptoms and other clinical characteristics in patients with chronic obstructive pulmonary disease (COPD), and to look for related risk factors affecting morning symptoms.MethodsThis cross-sectional observational study included 153 patients with stable COPD. Morning symptoms were evaluated with the Chinese-version of Chronic Obstructive Pulmonary Disease Morning Symptom Diary (Ch-COPD-MSD). And modified version of the British medical association respiratory questionnaire (mMRC), COPD assessment test (CAT), questionnaire clinical COPD questionnaire (CCQ) score were scored, and the BODEx index was calculated.ResultsA total of 153 stable COPD patients were included. The patients aged 59.6±7.6 years with a mean forced expiratory volume in one second of (52.0±20.7)% predicted (FEV1%pred). The median score of morning symptoms was 31.00. Morning symptoms severity was different between GOLD groups A to D: median (interquartile range) score in GOLD A was 23.50 (20.00 - 27.25), in GOLD B was 31.00 (26.00 - 38.00), in GOLD C was 30.00 (23.75 - 35.75), and in GOLD D was 36.50 (27.00 - 47.50) (P<0.001). Meanwhile, under different mMRC, CAT, CCQ scores, the difference in the median score of morning symptoms was statistically significant (all P=0.000). Score of morning symptoms was negatively correlated with the FEV1%pred (r=–0.24, P<0.001), and positively correlated with the score of mMRC, CAT, CCQ, and the BODEx index (r value was 0.50, 0.60, 0.53, 0.40, respectively, P<0.001). Multiple linear regression analysis showed that CAT score was the important factor associated with morning symptoms severity in COPD (B=0.829, P<0.001).ConclusionsMorning symptoms are associated with multiple clinical indicators for assessing the severity of COPD, and health status is the most strongly associated with morning symptoms. Clinical evaluation of morning symptoms in patients with COPD can be helpful in comprehensive assessment of the patient’s condition.