To explore the mechanism of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma herbal pair in reducing hypertensive renal damage by regulating miR-466b-5p.Methods:The differential genes between spontaneously hypertensive rats(SHR) and Wistar-Kyoto(WKY) rats were found by miRNA sequencing to construct adeno-associated virus-transfected rats.Twelve out of 24 C57BL/6 mice were randomly selected to be injected with adeno-associated virus miR-466b-5P(rAAV-miR-466b-5P) into the tail vein to construct a miR-466b-5p overexpression group，and the other 12 mice were assigned to the blank control group and were injected with AAV-9 empty carrier.Six weeks after the transfection，the two groups were randomly subdivided into two groups，with six mice in each group.Group A(Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma+miR-466b-5P overexpression group) and group C(Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma+blank control group) received Huangqi Formula Granules(2.036 g/kg) and Danshen Formula Granules(0.255 g/kg) by gavage.Group B(miR-466b-5P overexpression group) and group D(blank control group) were received the same volume of saline by gavage.After 28 d of intragastric administration，the urine β2-microglobulin(β2-MG)，N-acetyl-β-D-glucosidase(NAG)，microalbumin(mALB)，serum cystatin C(Cys-C)，angiotensin Ⅱ(AngⅡ)，and C-reactive protein(CRP) levels and renal pathology of mice were observed in each group，and Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western Blotting assay were performed to find the target genes.Results:1) MiR-466b-5p was selected based on previous miRNA sequencing. 2) The urine β2-MG，NAG，mALB，serum Cys-C，AngⅡ，and CRP levels in group B were higher than those in the group D(P<0.01).Compared with the results in group B，the serum Cys-C and CRP levels increased in group A(P<0.01)，while the urine β2-MG，NAG，mALB，and serum AngⅡ levels did not change significantly(P>0.05). 3) Compared with group D，group B showed significant glomerulosclerosis and tubular fibrosis，and group A showed significant improvement compared with group B. 4) The hyaluronidase 2(HAS2) was significantly down-regulated in group B，which was reversed after Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma intervention as compared with that in the group D.Conclusion:The overexpression of miR-466b-5p can cause hypertensive renal damage，and Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma can down-regulate miR-466b-5p by targeting HAS2 to reduce hypertensive renal damage.