中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (7): 539-550.DOI: 10.5246/jcps.2023.07.045
王番#, 李锐莉#, 王文军#, 周晓燕#, 刘美佑, 赵瑾怡, 文爱东, 王婧雯*(), 贾艳艳*()
收稿日期:
2022-11-17
修回日期:
2022-12-21
接受日期:
2023-03-09
出版日期:
2023-07-31
发布日期:
2023-07-31
通讯作者:
王婧雯, 贾艳艳
作者简介:
基金资助:
Fan Wang#, Ruili Li#, Wenjun Wang#, Xiaoyan Zhou#, Meiyou Liu, Jinyi Zhao, Aidong Wen, Jingwen Wang*(), Yanyan Jia*()
Received:
2022-11-17
Revised:
2022-12-21
Accepted:
2023-03-09
Online:
2023-07-31
Published:
2023-07-31
Contact:
Jingwen Wang, Yanyan Jia
About author:
摘要:
α-乳香酸(α-BA)是乳香药材经过提取、分离、纯化后的产物, 可用于治疗多种炎症性疾病。本研究旨在通过体内外实验评估α-BA在改善缺血再灌注损伤诱导的急性肾损伤中的作用。对大鼠进行右肾切除和左肾缺血再灌注损伤, 损伤前0.5 h给予α-BA处理。体内实验, 对组织进行肾功能、组织病理学和TUNEL染色分析。体外实验, 对近端肾小管细胞(HK-2)进行氧糖剥夺(OGD)操作, 以模仿缺血再灌注损伤, 并检测细胞存活率、免疫荧光染色及Toll样受体4(TLR4)和核因子(NF)-κB表达。结果显示, 给予α-BA的模型组大鼠血清肌酐和血尿素氮水平显著降低, 并缓解细胞凋亡和肾脏形态学改变; 经α-BA处理的HK-2细胞, NF-κBp6的表达明显降低。表明α-BA改善缺血再灌注损伤诱导的急性肾损伤, 部分原因是通过TLR4介导的炎症通路促进肾小管细胞存活, 从而改善肾功能。
Supporting:
王番, 李锐莉, 王文军, 周晓燕, 刘美佑, 赵瑾怡, 文爱东, 王婧雯, 贾艳艳. α-乳香酸通过抑制TLR4介导的炎症通路改善急性肾损伤[J]. 中国药学(英文版), 2023, 32(7): 539-550.
Fan Wang, Ruili Li, Wenjun Wang, Xiaoyan Zhou, Meiyou Liu, Jinyi Zhao, Aidong Wen, Jingwen Wang, Yanyan Jia. α-Boswellic acid ameliorates acute kidney injury by inhibiting the TLR4-mediated inflammatory pathway[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(7): 539-550.
Figure 1. Effect of α-BA on kidney function tests in IRI-induced AKI in rats. (A) Chemical structure of α-BA. (B, C) Increases in BUN and Scr levels at 24 h after IRI were abrogated by α-BA of different concentrations (n = 8 rats/group). *P < 0.05 vs. Sham; #P < 0.05 vs. IRI.
Figure 2. Effect of α-BA on kidney injury after IR administration. (A) Representative photomicrographs (H&E staining; magnification, 200×) of renal sections from rats under various experimental conditions. (B) Assessment of tubular injury.*P < 0.05 vs. Sham; #P < 0.05 vs. IRI.
Figure 3. α-BA pretreatment ameliorates tubular apoptosis induced by IRI in vivo. (A) Representative images (magnification, ×400) of renal TUNEL assay from rats subjected to sham, IRI, and IRI + α-BA. (B) The percentage of TUNEL-positive cells in kidney sections was increased following IRI and decreased following treatment with α-BA. *P < 0.05 vs. Sham; #P < 0.05 vs. IRI, n = 8.
Figure 4. α-BA pretreatment ameliorates tubular apoptosis induced by IRI in vitro. (A) Anti-apoptotic effects on HK-2 cells following OGD injury were confirmed by Hoechst 33258 staining. A quantitative analysis of apoptosis is shown in (B). Data were presented as mean ± SD and represented three independent experiments; *P < 0.05 vs. control; #P < 0.05 vs. OGD. (C) The effect of α-BA on HK-2 cell viability was tested by MTT assay. Cells in the sham group were considered 100% viable. Data were presented as mean ± SD (n = 3). *P < 0.05 vs. Sham; #P < 0.05 vs. OGD.
Figure 5. Effects of α-BA on activation of the TLR4 and NF-κB signaling pathway in IRI-induced AKI. Representative Western blots showing the effects of α-BA on TLR4 and NF-κB expression in the kidney after 40 min of ischemia followed by 24 h of reperfusion. α-Tubulin was used to show equal amounts of protein loading in each lane. (A) Representative Western blots showing the effects of α-BA on TLR4 and NF-κB p65 expression. (B) Relative band densities of TLR4 and (C) NF-κB p65 to the mean value of the control. *P < 0.05 vs. Sham; #P < 0.05 vs. IRI.
Figure 6. Effect of α-BA on TLR4 and NF-κB signaling pathway in OGD-induced HK-2 cells. HK-2 cells were incubated in the presence or absence of different concentrations of α-BA (10, 20, and 40 μM) for 24 h and then incubated with or without OGD for another 24 h. α-Tubulin was used to show equal amounts of protein loading in each lane. (A) The expression levels of TLR4 and NF-κB p65 in cell lysates were determined by Western blotting analysis. (B) Relative band densities of TLR4 and (C) NF-κB p65 to the mean value of the control. All data were presented as mean ± SD from three separate experiments. *P < 0.05 vs. Control; #P < 0.05 vs. OGD.
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