Renal Protective Effect of Tongxinluo Submicron Powder on Mice with Diabetic Kidney Disease Based on PANoptosis
10.13422/j.cnki.syfjx.20260635
- VernacularTitle:基于泛凋亡探讨通心络超微粉对糖尿病肾病小鼠的肾脏保护作用
- Author:
Huinan XU
1
;
Haorui XU
2
;
Tao LIU
1
;
Shuang SHEN
1
Author Information
1. School of Traditional Chinese Medicine， Nanjing University of Chinese Medicine， Nanjing 210000， China
2. The First School of Clinical Medicine， Nanjing University of Chinese Medicine， Nanjing 210000， China
- Publication Type:Journal Article
- Keywords:
diabetic kidney disease;
BKS-db;
Nos3KO mice;
Tongxinluo submicron powder;
PANoptosis;
renal protection
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(17):155-163
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role and underlying mechanisms of Tongxinluo submicron powder in regulating renal PANoptosis， alleviating pathological injury in diabetic kidney disease （DKD）， reducing urinary albumin excretion， and improving renal function in DKD mice. MethodsSix 6-week-old male C57BL/Ks mice were assigned into the normal group. Eighteen 6-week-old male BKS-db；Nos3KO mice were randomly divided into three groups： model group， Tongxinluo group （0.75 g·kg-1·d-1）， and dapagliflozin group （0.001 g·kg-1·d-1）， and were administered by gavage for 12 consecutive weeks. General conditions of the mice were observed. At weeks 0， 4， 8， and 12 after administration， body weight， fasting blood glucose （FBG）， urine albumin-to-creatinine ratio （UACR）， and urinary albumin excretion rate （AER） were measured. After treatment， mice were anesthetized for sample collection. Blood was obtained by orbital enucleation and centrifuged to collect supernatant. Serum creatinine （SCr）， urea （UREA）， β2-microglobulin （β2-MG）， retinol-binding protein （RBP）， and serum cystatin C （CysC） were measured. Renal histopathological changes were evaluated using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of inflammatory cytokines， including interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α）. Serum levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） were also measured. Western blot analysis was performed to quantify the expression of key PANoptosis-related proteins in renal tissue， including Z-DNA-binding protein 1 （ZBP1）， Caspase-1， cleaved Caspase-1， gasdermin D （GSDMD） and its N-terminal fragment （GSDMD-N）， Caspase-8， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， mixed lineage kinase domain-like protein （MLKL）， and phosphorylated MLKL （p-MLKL）. ResultsCompared with the normal group， the model group showed significant obesity and continuously increased blood glucose levels （P<0.05）. Renal function indicators （UREA， β2-MG， CysC） were significantly increased （P<0.05）， and urinary albumin excretion indicators （UACR， AER） were markedly elevated （P<0.05）. Renal histopathology showed enlarged glomeruli， diffuse thickening of the basement membrane， and significant expansion of the mesangial matrix. Masson staining revealed extensive blue collagen fiber deposition， suggesting glomerulosclerosis and interstitial fibrosis. Meanwhile， serum levels of inflammatory cytokines （IL-1β， IL-18， and TNF-α） were significantly increased （P<0.05）. SOD and GSH-Px levels were decreased， while MDA levels were increased （P<0.05）. The expression of key PANoptosis-related proteins （ZBP1， cleaved Caspase-1， GSDMD， GSDMD-N， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， and p-MLKL） in renal tissue was significantly upregulated （P<0.05）. After intervention， compared with the model group， renal function indicators （UREA， β2-MG， CysC） and urinary albumin excretion indicators （UACR， AER） in the Tongxinluo group were significantly decreased （P<0.05）， and all were superior to those in the dapagliflozin group （P<0.05）. Renal pathological injury was markedly alleviated， with reduced mesangial proliferation and collagen fiber deposition. In addition， serum levels of IL-1β， IL-18， and TNF-α were significantly decreased （P<0.05）. SOD and GSH-Px levels were increased， while MDA levels were decreased （P<0.05）. Western blot results showed that the expression of key PANoptosis-related proteins （ZBP1， cleaved Caspase-1， GSDMD， GSDMD-N， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， and p-MLKL） in renal tissue was significantly downregulated （P<0.05）. ConclusionTongxinluo submicron powder can inhibit renal PANoptosis in DKD mice， alleviate renal inflammatory response and pathological injury， reduce urinary albumin excretion， and improve renal function.
