商陆总皂苷对癌性腹水模型小鼠的祛腹水作用及机制初探  

Anti-ascites effect of total saponins of Phytolaccae Radix on mice with ascites and mechanism

作　　者：王彩霞 郁红礼[1,2,3] 吴皓[1,2,3] 陶兴宝 谢雨薇 程砚秋 曾平 王贺鹏 张萍[4] 崔小兵[1] WANG Cai-xia;YU Hong-li;WU Hao;TAO Xing-bao;XIE Yu-wei;CHENG Yan-qiu;ZENG Ping;WANG He-peng;ZHANG Ping;CUI Xiao-bing(School of Pharmacy,Nanjing Universiy of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory of Chinese Medicine Processing,Nanjing 210023,China;Engineering Center of Stale Ministry of Education for Standardization of Chinese Medicine Processing,Nanjing 210023,China;National Institutes for Food and Drug Control,Bejing 100050,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药炮制重点实验室,江苏南京210023 [3]国家教育部中药炮制规范化及标准化工程研究中心,江苏南京210023 [4]中国食品药品检定研究院,北京100050

出　　处：《中国中药杂志》2022年第16期4411-4417,共7页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1707000);江苏省高等学校自然科学研究重大项目(20KJA360003);江苏省研究生培养创新工程项目(KYCX21_1751)。

摘　　要：为研究商陆皂苷类成分祛腹水药效作用及其机制,采用H22腹水小鼠模型,取ICR雄性小鼠腹腔注射H22细胞混悬液,将造模成功小鼠随机分为模型组、阳性药组(呋塞米,6 mg·kg^(-1))、商陆总提物组和总皂苷组(1.29 g·kg^(-1)),另取雄性小鼠10只作为空白组。空白组和模型组小鼠灌胃给予含0.5%CMC-Na的生理盐水,阳性药组、商陆总提物组和总皂苷组小鼠灌胃给予相应剂量药物,每日1次,连续给药8 d,考察商陆总皂苷对模型小鼠腹水量、给药后5 h内尿量和粪便含水量的影响,同时以血清抗利尿激素(ADH)、肾素-血管紧张素-醛固酮系统(RAAS)相关激素肾素(renin)、血管紧张素2(AngⅡ)和醛固酮(ALD)含量,肾脏组织中水通道蛋白(aquaporin,AQP)1~AQP4表达量,结肠AQP1、AQP3表达量及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)通路相关蛋白的表达量为指标,探索商陆总皂苷祛腹水作用的机制。结果表明,商陆总皂苷可以增加腹水模型小鼠尿量和粪便含水量,减少腹水量;显著降低肾脏AQP1~AQP4和结肠AQP1、AQP3的表达;显著降低血清ADH、renin、AngⅡ和ALD水平;同时可显著降低腹水模型小鼠肾脏p-PI3K和p-Akt蛋白的表达。商陆总皂苷通过利尿和泻下作用发挥祛腹水功效,其作用机制可能与抑制RAAS、ADH活性;抑制PI3K/Akt信号通路磷酸化从而抑制肾脏和结肠AQPs表达有关。This study investigated the anti-ascites effect of the total saponins of Phytolaccae Radix(PRTS)and the mechanism.H22 cell suspension was used(ip)to induce ascites in ICR male mice,and the model mice were randomized into model group,positive drug group(furosemide,6 mg·kg^(-1)),total extract of Phytolaccae Radix(PRTE)group,and PRTS(1.29 g·kg^(-1)).Another 10 male mice were selected as the blank group.Mice in the blank group and model group were given(ig)normal saline containing 0.5%CMC-Na,and those in the positive drug group,PRTE group,and PRTS group received(ig)corresponding doses of drugs,once a day,for 8 consecutive days.The ascites volume,urine volume,and fecal water content in mice with ascites,serum levels of antidiure-tic hormone(ADH),renin in renin-angiotensin-aldosterone system(RAAS),angiotensinⅡ(AngⅡ),and aldosterone(ALD),expression of aquaporin(AQP)1-AQP4 in kidney,expression of AQP1,AQP3 in colon,and expression of phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt)pathway-related proteins were detected to explore the anti-ascites mechanism of PRTS.The results showed that the PRTS can increase the urine volume and fecal water content and decrease the ascites volume of ascites mice.Moreover,PRTS significantly reduced the expression of AQP1-AQP4 in kidney and AQP1,AQP3 in colon,serum levels of renin,AngⅡ,ALD,and ADH,and the expression of p-PI3 K and p-Akt in the kidney of ascites mice.PRTS exerts anti-ascites effect by promoting urination and defecation.The mechanism is that it inhibits the activities of RAAS and ADH and suppresses the phosphorylation of PI3 K/Akt signaling pathway,thereby restricting the expression of AQPs in the kidney and colon.

关 键 词：商陆总皂苷 腹水 水通道蛋白 PI3K/Akt 肾素-血管紧张素-醛固酮系统(RAAS) 

分 类 号：R285.5[医药卫生—中药学]