Objective:

2

To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD).

Methods:

2

The db/db mice were divided into model group and MHW group according to a random number table

while db/m mice were settled as the control group (

n

=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg•d)

]

and the MHW group was treated with MHW [17.8 g/(kg•d)

]

for 6 weeks. After MHW administration for 6 weeks

indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay

Western blot analysis

immunohistochemistry

and immunofluorescence staining.

Results:

2

Compared with the model group

MHW improved glucose and lipid metabolism (

P

<

0.05)

and reduced lipid deposition in the kidney. Meanwhile

MHW reduced the excretion of urinary albumi

n (

P

<

0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response

particularly the interleukin-17 (IL-17) signaling pathway

may be responsible for the effect of MHW on DKD. Furtherly

our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney.

Conclusion:

2

MHW ameliorated renal damage in DKD via inhibiting IL-17A

suggesting a potential strategy for DKD therapy.