Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, People's Republic of China.
Drug Des Devel Ther. 2022 Aug 26;16:2851-2860. doi: 10.2147/DDDT.S363974. eCollection 2022.
In this study, the HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β1 (TGF-β1) signaling pathway.
Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15.
LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated.
These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 10 CFU/kg.
本研究对从自然发酵牦牛酸奶中分离得到的 HFY15（LP-HFY15）菌株进行了研究。通过用 pristane 建立狼疮肾炎动物模型，验证 LP-HFY15 通过调节转化生长因子-β1（TGF-β1）信号通路对狼疮肾炎小鼠的干预作用。
试剂盒检测小鼠血清和组织中的指标，苏木精-伊红（H&E）染色观察小鼠肾脏的病理变化，定量聚合酶链反应（qPCR）检测小鼠肾脏组织中 TGF-β1 相关表达，进一步阐明 LP-HFY15 的作用机制。
LP-HFY15 降低了狼疮肾炎小鼠尿蛋白及血清和肾组织中白细胞介素-6（IL-6）、白细胞介素-12（IL-12）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平。LP-HFY15 还降低了肾炎小鼠血清肌酐（SCr）、血尿素氮（BUN）、总胆固醇（TC）、甘油三酯（TG）水平，提高了总蛋白（TP）和白蛋白（ALB）水平。此外，LP-HFY15 抑制了肾炎小鼠双链脱氧核糖核酸（dsDNA）抗体的阳性率。H&E 切片观察结果显示，LP-HFY15 减轻了肾炎引起的肾小球形态不完整和炎症浸润。进一步的结果表明，LP-HFY15 下调了狼疮肾炎小鼠肾脏中 TGF-β1、血管内皮生长因子（VEGF）和核因子-κB（NF-κB）的 mRNA 表达，同时上调了 NF-κB 抑制剂（IκB-α）、铜/锌超氧化物歧化酶（Cu/Zn-SOD）和锰超氧化物歧化酶（Mn-SOD）的表达。
这些结果表明，LP-HFY15 在狼疮肾炎的实验干预中发挥了重要作用。LP-HFY15 的作用与浓度呈正相关，其作用与 10 CFU/kg 泼尼松相似。
