Li Ying, An Mingli, Fu Xinping, Meng Xin, Ma Yiming, Liu Huimin, Li Qingxue, Xu Huazhou, Chen Jingwei
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, PR China.
Department of Gynecology, The Fourth Hospital of Shijiazhuang City, Shijiazhuang, Hebei, 050011, PR China.
J Ethnopharmacol. 2023 May 23;308:116277. doi: 10.1016/j.jep.2023.116277. Epub 2023 Feb 17.
Bushen Wenyang Huayu Decoction (BWHD) is a traditional Chinese medicine for tonifying kidney and warming Yang, thereby resolving blood stasis and relieving pain. BWHD can significantly improve the clinical symptoms of patients with endometriosis (EMs), but its mechanism is still unclear.
We evaluated the expression and role of the SIRT1-FoxO-1 pathway and autophagy levels in EMs rats. The therapeutic effects and potential therapeutic mechanisms of BWHD were also investigated.
Twenty rats were randomized into the sham group and eighty rats were used for model establishment by autologous transplantation. After successful modeling, they were randomized into the model, BWHD, EX527+BWHD and EX527 groups, with 20 rats in each group. All rats were intragastrically administered with for 3 weeks. Localization of Sirtuin 1 (SIRT1), Forkhead boxO-1 (FoXO-1), Beclin-1, autophagy-related 5 (Atg5) and autophagy-related 7 (Atg7) was determined by immunohistochemical staining. The expression of the above proteins was determined by Western blot and their messenger RNA (mRNA) levels were detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).
The protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in the model group were markedly increased, while that of SIRT1 was markedly decreased relative to the sham group (p < 0.05 and p<0.01, respectively). Results showed that the protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of BWHD group were lower, while SIRT1 expression was higher than in the model group (p < 0.05 and p<0.01, respectively). Furthermore, protein and mRNA expression levels of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of EX527 group were higher, while SIRT1 level was significantly lower than in the model group (p < 0.05 and p < 0.01, respectively). The EX527-induced changes in protein and mRNA expressions were reversed in the EX527+BWHD group (p < 0.05 and p < 0.01, respectively).
BWHD inhibits autophagy by up-regulating SIRT1 and down-regulating FoXO-1 expression in EMs via the SIRT1-FoXO-1 signaling pathway. Therefore, it is a potential treatment for EMs.
补肾温阳化瘀汤（BWHD）是一种用于补肾壮阳、化瘀止痛的中药。BWHD可显著改善子宫内膜异位症（EMs）患者的临床症状，但其机制仍不清楚。
我们评估了SIRT1-FoxO-1信号通路的表达及作用以及EMs大鼠的自噬水平。还研究了BWHD的治疗效果和潜在治疗机制。
将20只大鼠随机分为假手术组，80只大鼠用于自体移植建立模型。建模成功后，将它们随机分为模型组、BWHD组、EX527+BWHD组和EX527组，每组20只大鼠。所有大鼠均灌胃给药3周。通过免疫组织化学染色确定沉默调节蛋白1（SIRT1）、叉头框O-1（FoXO-1）、Beclin-1、自噬相关蛋白5（Atg5）和自噬相关蛋白7（Atg7）的定位。通过蛋白质印迹法测定上述蛋白的表达，并通过定量实时聚合酶链反应（qRT-PCR）检测它们的信使核糖核酸（mRNA）水平。
与假手术组相比，模型组中FoXO-1、Beclin-1、Atg5和Atg7的蛋白和mRNA表达显著增加，而SIRT1的表达显著降低（分别为p < 0.05和p < 0.01）。结果显示，BWHD组在位和异位内膜中FoXO-1、Beclin-1、Atg5和Atg7的蛋白和mRNA表达较低，而SIRT1表达高于模型组（分别为p < 0.05和p < 0.01）。此外，EX527组在位和异位内膜中FoXO-1、Beclin-1、Atg5和Atg7的蛋白和mRNA表达水平较高，而SIRT1水平显著低于模型组（分别为p < 0.05和p < 0.01）。EX527诱导的蛋白和mRNA表达变化在EX527+BWHD组中得到逆转（分别为p < 0.05和p < 0.01）。
BWHD通过SIRT1-FoXO-1信号通路上调SIRT1并下调EMs中FoXO-1的表达来抑制自噬。因此，它是一种治疗EMs的潜在药物。
