鹿苓安肾颗粒对慢性肾功能衰竭大鼠炎症反应及细胞凋亡的影响

doi:10.6040/j.issn.1671-7554.0.2023.0050

摘要/Abstract

摘要： 目的探讨鹿苓安肾颗粒对腺嘌呤诱导的慢性肾功能衰竭(CRF)大鼠的影响及其潜在机制。方法将SD雄性大鼠分成6组:对照组,模型组,阳性药物组(尿毒清颗粒,2.25 g/kg),鹿苓安肾颗粒低、中、高剂量组(2.5、5、10 g/kg),每组10只。除对照组外,其他各组大鼠均采用灌胃2.5%腺嘌呤混悬液建立CRF大鼠模型,造模成功后给予相应药物灌胃干预,1次/d,连续28 d。观察并记录大鼠一般情况;腹主动脉取血,测定血清中血尿素氮(BUN)和血肌酐(Scr)水平和24 h尿蛋白水平;酶联免疫吸附测定法(ELISA)检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平;苏木精-伊红(HE)染色观察肾脏组织病理学变化;免疫组化检测肾脏组织中碱性成纤维细胞生长因子(bFGF)水平;实时荧光定量PCR(qRT-PCR)和Western blotting检测肾脏组织中Bax、Bcl-2和Caspase-3 mRNA及Bax、Bcl-2和Cleaved-Caspase-3蛋白表达水平。结果与对照组比较,模型组大鼠肾脏组织损伤严重,24 h尿蛋白水平,血清中BUN、Scr、IL-1β、IL-6和TNF-α水平,肾脏组织中Bax/Bcl-2、Caspase-3 mRNA及Bax/Bcl-2和Cleaved-Caspase-3蛋白表达水平及bFGF水平均明显上升(P<0.05)。与模型组比较,鹿苓安肾颗粒低、中、高剂量组和阳性药物组大鼠肾脏组织损伤均明显减轻,24 h尿蛋白水平,血清中BUN、Scr、IL-1β、IL-6和TNF-α水平,肾脏组织中Bax/Bcl-2、Caspase-3 mRNA及Bax/Bcl-2和Cleaved-Caspase-3蛋白表达水平及bFGF水平均明显下降(P<0.05),且呈剂量依赖性。结论鹿苓安肾颗粒可抑制CRF大鼠肾脏组织炎症反应、细胞凋亡和纤维化,改善肾功能,从而对CRF大鼠肾脏具有一定的保护作用。

关键词: 慢性肾功能衰竭, 鹿苓安肾颗粒, 炎症反应, 细胞凋亡, 肾纤维化

Abstract: Objective To investigate the effects of Luling Anshen Granule on adenine-induced chronic renal failure(CRF)rats and its potential mechanism. Methods Male SD rats were divided into 6 groups: control group, model group, positive drug group(Niaoduqing Granule, 2.25 g/kg), low-, medium- and high-dose Luling Anshen Granule groups(2.5, 5, 10 g/kg), with 10 rats in each group. Except the control group, the other groups were given 2.5% adenine suspension by gavage to establish CRF models, and corresponding drugs were given by gavage once a day for a consecutive of 28 days after successful modeling. The general condition of rats was observed and recorded. Blood was sampled from the abdominal aorta to measure the levels of blood urea nitrogen(BUN)and serum creatinine(Scr), and the level of 24-hour urinary protein was also measured. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum were determined with ELISA. Histopathological changes of kidney tissues were observed with HE staining. The level of basic fibroblast growth factor(bFGF)in renal tissues was detected with immunohistochemistry. The mRNA expressions of Bax, Bcl-2 and Caspase-3, and the protein expressions of Bax, Bcl-2 and Cleaved-Caspase-3 in renal tissues were detected with qRT-PCR or Western blotting. Results Compared with the control group, the model group had more serious renal injury, and significantly increased levels of 24-hour urinary protein, BUN, Scr, IL-1β, IL-6, TNF-α, mRNA expressions of Bax/Bcl-2 and Caspase-3, protein expressions of Bax/Bcl-2 and Cleaved-Caspase-3, and bFGF(P<0.05). Compared with the model group, the Luling Anshen Granule intervention groups and positive drug group had significantly alleviated renal injury, and significantly decreased levels of the above indexes in a dose-dependent manner(P<0.05). Conclusion Luling Anshen Granule can inhibit the inflammatory response, cell apoptosis and fibrosis in kidney tissues of CRF rats and improve the renal function, thus having a protective effect on the kidney.

Key words: Chronic renal failure, Luling Anshen Granule, Inflammatory response, Cell apoptosis, Renal fibrosis

中图分类号:

R285.5

杨元凤,熊高才,黎豫川,罗玉玲,张敬杰. 鹿苓安肾颗粒对慢性肾功能衰竭大鼠炎症反应及细胞凋亡的影响[J]. 山东大学学报 (医学版), 2023, 61(10): 9-16.

YANG Yuanfeng, XIONG Gaocai, LI Yuchuan, LUO Yuling, ZHANG Jingjie. Effects of Luling Anshen Granule on the inflammatory response and cell apoptosis in rats with chronic renal failure[J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 9-16.

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