Ruiqi Liu, Ming Pei, Qihang Su, Yangyang Lei, Junli Chen, Wei Lin, Chao Gao, Xinyue Liu, Kang Yang, Hongtao Yang
Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.
Renal Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Front Pharmacol. 2021 Oct 1;12:628671. doi: 10.3389/fphar.2021.628671. eCollection 2021.
Peritoneal dialysis (PD) can improve the quality of life of patients with kidney disease and prolong survival. However, peritoneal fibrosis can often occur and lead to PD withdrawal. Therefore, it is imperative to better understand how to inhibit and slow down progression of peritoneal fibrosis. This study aimed to investigate the regulatory effect of Saikosaponin d (SSD), a monomer extracted from the plant Bupleurum, on peritoneal fibrosis and the contribution of TGFβ1/BMP7/Gremlin1 pathway cross-talk in this process. To this aim, we used a model 5/6 nephrectomy and peritoneal fibrosis in rats. Rats were divided into four groups, namely a control group (saline administration); a model group (dialysate administration; group M); a SSD group (dialysate and SSD administration); and a positive drug group (dialysate and Benazepril Hydrochloride administration; group M + A). Histological analysis indicated that peritoneal fibrosis occurred in all groups. WB, ELISA, and PCR essays suggested that TGFβ1 and Gremlin1 levels in group M were significantly higher than those in group C, whereas BMP7 expression was significantly lower. TGFβ1, Gremlin1 and BMP7 levels were significantly lower in the group where SSD was administered than in the other groups. The expression of BMP7 in SSD group was significantly increased. In addition, levels of Smad1/5/8 as assessed by PCR, and levels of p-Smad1/5/8 expression as assessed by WB were also significantly higher in the SSD group than in the M group. Expression of vimentin and α-SMA, two important markers of fibrosis, was also significantly decreased. Our study suggests a role for the TGFβ1/BMP7/Gremlin1/Smad pathway in peritoneal fibrosis with potential therapeutic implications. Finally, our results also suggest that the monomer SSD may be able to reverse peritoneal fibrosis regulation of the TGFβ1/BMP7/Gremlin1/Smad pathway.
腹膜透析（PD）可改善肾病患者的生活质量并延长生存期。然而，腹膜纤维化常常发生并导致腹膜透析终止。因此，必须更好地了解如何抑制和减缓腹膜纤维化的进展。本研究旨在探讨从植物柴胡中提取的单体柴胡皂苷d（SSD）对腹膜纤维化的调节作用以及TGFβ1/BMP7/Gremlin1信号通路串扰在此过程中的作用。为此，我们采用大鼠5/6肾切除和腹膜纤维化模型。大鼠分为四组，即对照组（给予生理盐水）；模型组（给予透析液；M组）；SSD组（给予透析液和SSD）；以及阳性药物组（给予透析液和盐酸贝那普利；M+A组）。组织学分析表明，所有组均发生了腹膜纤维化。蛋白质免疫印迹法（WB）、酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）检测表明，M组中TGFβ1和Gremlin1水平显著高于C组，而BMP7表达显著降低。给予SSD组的TGFβ1、Gremlin1和BMP7水平显著低于其他组。SSD组中BMP7的表达显著增加。此外，通过PCR评估的Smad1/5/8水平以及通过WB评估的p-Smad1/5/8表达水平在SSD组中也显著高于M组。波形蛋白和α-平滑肌肌动蛋白（α-SMA）这两种重要的纤维化标志物的表达也显著降低。我们的研究表明TGFβ1/BMP7/Gremlin1/Smad信号通路在腹膜纤维化中发挥作用，具有潜在的治疗意义。最后，我们的结果还表明单体SSD可能能够通过调节TGFβ1/BMP7/Gremlin1/Smad信号通路来逆转腹膜纤维化。
