四君子汤对慢性肾脏病-蛋白质能量消耗模型小鼠的改善作用及机制研究
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篇名: 四君子汤对慢性肾脏病-蛋白质能量消耗模型小鼠的改善作用及机制研究
TITLE: Study on the Improvement Effects of Sijunzi Decoction on Chronic Kidney Disease-protein Energy Wasting Model Mice and Its Mecranism
摘要: 目的:研究四君子汤对慢性肾脏病-蛋白质能量消耗(CKD-PEW)模型小鼠骨骼肌萎缩的改善作用,并探讨其可能的作用机制。方法:将80只小鼠随机分为假手术组(n=10)和造模组(n=70)。造模组小鼠采用切除5/6肾联合低蛋白(4%酪蛋白)饮食法建立CKD-PEW模型。将造模成功的50只小鼠随机分为模型组,四君子汤低、中、高剂量组[2.34、4.68、9.36g/(kg·d),以生药量计]和复方α-酮酸片组[阳性对照,1g/(kg·d)],每组10只。各给药组小鼠灌胃相应药物,假手术组和模型组小鼠灌胃等体积生理盐水,每天1次,连续灌胃14d。末次给药后,称定小鼠体质量、左侧胫骨前肌(TA)湿质量,并测定TA横截面积;检测小鼠TA蛋白合成与分解代谢情况;采用实时荧光定量-聚合酶链式反应法检测小鼠TA中B淋巴细胞瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)及胱天蛋白酶3(Caspase-3)mRNA表达水平;采用Westernblotting法检测小鼠TA中肌萎缩蛋白Fbox-1(Atrogin-1)、肌环指蛋白1(MuRF-1)、Rho相关蛋白激酶1(ROCK1)、磷酸化肿瘤抑制基因(p-PTEN)、磷脂酰肌醇3激酶(PI3K)及磷酸化蛋白激酶B(p-Akt)蛋白的表达水平。结果:与假手术组比较,模型组小鼠的体质量、TA湿质量、TA蛋白合成代谢能力以及PI3K、p-Akt蛋白表达水平显著降低(P<0.05),TA横截面积显著减小(P<0.05),TA蛋白分解代谢能力、Bax/Bcl-2比值、Caspase-3mRNA表达水平和Atrogin-1、MuRF-1、ROCK1、p-PTEN蛋白表达水平显著升高(P<0.05)。与模型组比较,四君子汤中、高剂量组和复方α-酮酸片组小鼠上述指标均显著改善(P<0.05)。结论:四君子汤能够增加CKD-PEW模型小鼠体质量,抑制其骨骼肌萎缩;其机制可能与调控ROCK1/PTEN/Akt信号通路,抑制Atrogin-1和MuRF-1表达有关。
ABSTRACT: OBJECTIVE:To study the improvement effects of Sijunzi decoction on skeletal muscle atrophy in chronic kidney disease-protein energy wasting (CKD-PEW)model mice ,and to explore its potential mechanism . METHODS :A total of 80 mice were randomly divided into sham operation group (n=10)and modeling group (n=70). CKD-PEW model was established by removing 5/6 kidneys and giving a low-protein diet (4% casein)for mice in modeling group. Totally 50 modeled mice were randomly divided into model group ,Sijunzi decoction low-dose ,medium-dose and high-dose groups [ 2.34,4.68,9.36 g/(kg·d), by crude drug] ,Compound α-ketoacid tablets group [positive control ,1 g/(kg·d)],with 10 mice in each group. Administration groups were given relevant medicine intragastrically ;sham operation group and model group were given constant volume of normal saline intragastrically ,once a day ,for consecutive 14 d. After last medication ,body weight of mice and wet mass of left tibialis anterior muscle (TA)were weighed ;TA cross-sectional area was determined ;protein synthesis and decomposition metabolism ability of TA were detected ;mRNA expressions of Bcl-2,Bax and Caspase-3 in TA were detected by Real-time PCR ;protein expressions of muscular dystrophin Fbox- 1 (Atrogin-1),myofloin-1 (MuRF-1),Rho-related protein kinase 1 (ROCK1), phosphorylated PTEN (p-PTEN),phosphatidylinositol-3-kinase(PI3K)and phosphorylated Akt (p-Akt)in TA were detected by Western blotting. RESULTS :Compared with the sham operation group ,the body weight ,TA wet weight ,protein synthesis metabolism ability of TA as well as protein expressions of PI 3K and p-Akt were decreased significantly in model group (P<0.05); the cross-sectional area of TA decreased significantly (P<0.05);protein decomposition metabolism ability of TA ,Bax/Bcl-2 ratio, Caspase-3 mRNA expression ,protein expressions of Atrogin- 1,MuRF-1,ROCK1 and p-PTEN were increased significantly (P< 0.05). Compared with model group ,above indexes of mice were all improved significantly in Sijunzi decoction medium-dose , high-dose groups and Compound α-ketoacid tablets group (P<0.05). CONCLUSIONS :Sijunzi decoction can increase the body weight of CKD-PEW model mice and alleviate the skeletal atrophy ;the mechanism may be related to regulating ROCK 1/PTEN/Akt signaling pathway activity ,inhibiting the expression of Atrogin- 1 and MuRF- 1.
期刊: 2020年第31卷第19期
作者: 许烨,李志明,远方
AUTHORS: XU Ye,LI Zhiming ,YUAN Fang
关键字: 四君子汤;慢性肾脏病;蛋白质能量消耗;Rho相关蛋白激酶 1;磷酸化肿瘤抑制基因;磷脂酰肌醇-3-激酶;蛋白激酶B;
KEYWORDS: Sijunzi decoction ;Chronic kidney disease ;Protein energy wasting ;Rho-related protein kinase 1;PTEN;
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