心力衰竭是一個擁有 3 800 萬患者的全球化難題，而且這個數(shù)字隨著人口老齡化而增加。心力衰竭是 65 歲以上入院患者中最常見疾病，并多發(fā)于高收入國家。每年因心力衰竭而住院的患者高達 100 萬。目前藥物治療是臨床中治療心力衰竭的最主要方式，但傳統(tǒng)藥物治療效果有限。探求新的治療方法成為基礎和臨床研究的焦點。
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(yǎng)。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(xù)應用改良高脂飼料喂養(yǎng)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(shù),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(shù)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(fā)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(fā)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.
大面積腦梗死伴惡性腦水腫患者臨床預后差，即使經(jīng)過積極的內(nèi)科治療，仍有較高病死率。目前國內(nèi)外指南均推薦對符合指征的大面積腦梗死患者行外科減壓術治療，但缺乏操作性強的規(guī)范化診治流程和方案。重癥腦梗死研究協(xié)作組在循證醫(yī)學原則指導下，根據(jù)本協(xié)作組近年研究和試用的診治規(guī)范，提出大面積腦梗死惡性腦水腫外科減壓術規(guī)范化治療建議草案。