Qihuang Jianpi Zishen Granules (QJZG), a traditional Chinese medicine (TCM) formulation, is an approved hospital-prepared prescription clinically employed to enhance the therapeutic efficacy of prednisone (Pred) in the management of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Although the synergistic therapeutic effect of QJZG combined with Pred is well documented, the underlying molecular and immunological mechanisms remain to be fully elucidated.

Systemic lupus erythematosus (SLE) is a chronic inflammatory connective tissue disease caused by immune system dysfunction. The kidney, as one of the most frequently affected target organs, holds significant clinical importance during the course of the disease. Lupus nephritis (LN) is the most serious organ complication of SLE, and its progression to renal fibrosis is the main cause of end-stage renal disease. Studies have shown that Qihuang Jianpi Zishen Granules (QJZG) is a safe and effective traditional Chinese medicine preparation for treating lupus nephritis (LN), and the potential mechanism of its intervention in renal fibrosis of LN needs to be further explored. Therefore, this study proposes the hypothesis that lncRNA NEAT1 acts as a ceRNA sponge to adsorb miR-146a, thereby relieving its inhibitory effect on downstream Smad2. MRL/lpr mice and human glomerular mesangial cells were selected to study the effect of Qihuang Jianpi Zishen Granules (QJZG) on LN renal fibrosis. 

Our research found that Qihuang Jianpi Zishen Granules (QJZG) can significantly reverse the imbalance in the expression of lncRNA NEAT1/miR-146a-3p/Smad2 axis, inhibit the phosphorylation level of Smad2, and reduce the expression levels of serum inflammatory factors and renal fibrosis-related proteins. It also inhibits the proliferation of glomerular mesangial cells and the pathological process of LN renal fibrosis. 

The final results emphasize the role of the lncRNA NEAT1/miR-146a/Smad2 signaling axis in LN renal fibrosis and confirm that Qihuang Jianpi Zishen Granules (QJZG) exerts its therapeutic effect by interfering with this axis.