Lai Jun, Wu Yingzhi, Hang Liwei, Gael Akindavyi, Deng Ting, Yan Quanneng, Fu Qiang, Li Zhiliang
Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jan 30;39(1):113-119. doi: 10.12122/j.issn.1673-4254.2019.01.18.
To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism.
Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium.
Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment.
Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
探讨真武汤对尿毒症性心肌病大鼠心室肥厚的抑制作用并探究其机制。
将从乳鼠分离的心肌细胞分为对照组和硫酸吲哚酚（IS）组，采用[H]-亮氨酸掺入法检测蛋白质合成，并用蛋白质免疫印迹法检测细胞蛋白质表达。将50只SD大鼠随机分为假手术组、模型组、真武汤低剂量和高剂量治疗组，除假手术组大鼠外，其余大鼠均行5/6肾切除术。术后4周，真武汤低剂量和高剂量治疗组大鼠分别按4.5 g/kg和13.5 g/kg的剂量给予真武汤灌胃；假手术组和模型组大鼠给予等体积蒸馏水。治疗4周后，测定大鼠血清IS水平，测量大鼠心脏和心室质量指数；进行心脏超声检查，并用蛋白质免疫印迹法检测心肌中脑钠肽（BNP）、磷酸化细胞外信号调节激酶1/2（p-ERK1/2）、磷酸化p38丝裂原活化蛋白激酶（p-p38）和磷酸化c-Jun氨基末端激酶（p-JNK）的表达。
与对照细胞相比，IS处理的大鼠心肌细胞蛋白质合成显著增强，BNP、p-erk1/2和p-p38的表达水平升高（P<0.01），但两组之间p-jnk的表达相当。在动物实验中，与假手术组相比，模型组大鼠血清肌酐（SCr）、尿素氮（BUN）水平、24小时尿蛋白（24 hUpro）、血浆IS水平、左心室质量指数（LVMI）和全心质量指数（HMI）显著升高（P<0.01）；模型大鼠左室舒张末期内径（LVESD）和左室收缩末期内径（LVEDD）显著降低，左室前壁厚度（LVAWS）、左室后壁厚度（LVAWD）、左室后壁舒张期厚度（LVPWS）和左室后壁收缩期厚度（LVPWD）显著增加，同时出现明显的心肌细胞肥大，心肌中BNP、p-ERK1/2、p-p38和p-jnk的表达增加（P<0.01）。与模型组大鼠相比，真武汤低剂量和高剂量治疗组大鼠的SCr、BUN、24 hUpro和IS水平显著降低（P<0.05），LVMI和HMI降低；高剂量组LVESD、LVEDD、LVPWS、LVAWS和LVAWD改善更明显，治疗后心肌中BNP、p-ERK1/2、p-p38和p-JNK的表达显著下调。
真武汤可降低血浆IS水平，抑制心室肥厚，延缓尿毒症性心肌病大鼠的心室重构。
