Background. Better therapeutic drugs are required for treating hypertensive diabetic nephropathy. In our previous study, the Huaju Xiaoji (HJXJ) formula promoted the renal function of patients with diabetes and hypertensive nephropathy. In this study, we investigated the therapeutic effect and regulation mechanism of HJXJ in hypertensive diabetic mice with nephropathy. Methods. We constructed a mouse hypertensive diabetic nephropathy (HDN) model by treating mice with streptozotocin (STZ) and nomega-nitro-L-arginine methyl ester (LNAME). We also constructed a human glomerular mesangial cell (HGMC) model that was induced by high doses of sugar (30 mmol/mL) and TGFβ1 (5 ng/mL). Pathological changes were evaluated by hematoxylin and eosin (H&E) staining, periodic acid Schiff (PAS) staining, and Masson staining. The fibrosis-related molecules (TGFβ1, fibronectin, laminin, COL I, COL IV, α-SMA, and p-smad2/3) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression of endoplasmic reticulum stress, fibrosis molecules, and their downstream molecules were assessed using qPCR and Western blotting assays. Results. Administering HJXJ promoted the renal function of HDN mice. HJXJ reduced the expression of ER stress makers (CHOP and GRP78) and lncMGC, miR379, miR494, miR495, miR377, CUGBP2, CPEB4, EDEM3, and ATF3 in HDN mice and model HGMCs. The positive control drugs (dapagliflozin and valsartan) also showed similar effects after treatment with HJXJ. Additionally, in model HGMCs, the overexpression of CHOP or lncMGC decreased the effects of HJXJ-M on the level of fibrosis molecules and downstream target molecules. Conclusion. In this study, we showed that the HJXJ formula may regulate ERS-lncMGC/miRNA to enhance renal function in hypertensive diabetic mice with nephropathy. This study may act as a reference for further investigating whether combining HJXJ with other drugs can enhance its therapeutic effect. The findings of this study might provide new insights into the clinical treatment of hypertensive diabetic nephropathy with HJXJ.

中文翻译：

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化橘消积方调节ERS-lncMGC/miRNA增强高血压糖尿病肾病小鼠肾功能

背景。治疗高血压糖尿病肾病需要更好的治疗药物。在我们之前的研究中，化聚消积方可以促进糖尿病和高血压肾病患者的肾功能。本研究探讨了HJXJ对高血压糖尿病肾病小鼠的治疗作用及调节机制。方法。我们通过链脲佐菌素（STZ）和nomega-硝基-L-精氨酸甲酯（LNAME）治疗小鼠构建了小鼠高血压糖尿病肾病（HDN）模型。我们还构建了由高剂量糖（30 mmol/mL）和TGF β 1（5 ng/mL）诱导的人肾小球系膜细胞（HGMC）模型。通过苏木精和伊红（H&E）染色、高碘酸希夫（PAS）染色和马森染色评估病理变化。采用酶联免疫吸附试验（ELISA）检测纤维化相关分子（TGFβ1 、纤连蛋白、层粘连蛋白、COL I、COL IV、α -SMA、p-smad2/3）。使用 qPCR 和蛋白质印迹分析评估内质网应激、纤维化分子及其下游分子的 mRNA 水平和蛋白质表达。结果。服用HJXJ可促进HDN小鼠的肾功能。HJXJ 降低 HDN 小鼠和模型 HGMC 中 ER 应激因子（CHOP 和 GRP78）和 lncMGC、miR379、miR494、miR495、miR377、CUGBP2、CPEB4、EDEM3 和 ATF3 的表达。阳性对照药（达格列净和缬沙坦）在用活健消散治疗后也表现出类似的效果。此外，在HGMC模型中，CHOP或lncMGC的过表达降低了HJXJ-M对纤维化分子和下游靶分子水平的影响。结论。在这项研究中，我们发现HJXJ方可能通过调节ERS-lncMGC/miRNA来增强高血压糖尿病肾病小鼠的肾功能。本研究可为进一步探讨HJXJ与其他药物联合应用是否能增强其治疗效果提供参考。本研究的结果可能为HJXJ临床治疗高血压糖尿病肾病提供新的见解。