Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

Lupus nephritis (LN), one of the most severe complications of systemic lupus erythematosus (SLE), has a complex pathogenesis involving various endogenous factors including autoimmune complex deposition, inflammatory cell infiltration, and cellular damage. Recent research has increasingly highlighted the prominent role of inflammasomes, particularly the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, in LN pathogenesis. Substantial evidence has confirmed its significant role in both the onset and progression of LN. Given that the NLRP3 inflammasome is a critical factor in triggering and exacerbating LN, its mechanism of action warrants in-depth exploration. Furthermore, research on intervention strategies targeting the NLRP3 inflammasome to ameliorate LN is of great significance. This article reviews the latest advances in the role of the NLRP3 inflammasome in LN pathogenesis and related intervention studies, which may offer new insights for the clinical diagnosis and treatment of LN.
Humans ; Lupus Nephritis/etiology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/immunology* ; Animals

Objective To observe the effect of stageⅢdiabetic nephropathy(DN)treated by Qizhi Jiangtang capsule and explore its potential mechanism. Methods According to digital table method,the patients who conformed to the diagnostic criteria of stageⅢDN were randomly divided into two groups:an experiment group and a control group. All the patients in the two groups took elution treatment for 2 weeks,and then were treated with western basic therapy. The patients in the experiment group were administered orally with Qizhi Jiangtang capsule(2.5 g once, 3 times a day),while those in the control group treated with valsartan 80 mg,once a day. Urine microalbumin(mALB), mALB/urine creatinine(UCr),β2-microglobulin(β2-MG),α1-microglobulin(α1-MG)were observed in the two groups,endothelin-1(ET-1),nitric oxide(NO),thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) were also determined. Serum creatinine(SCr),blood urea nitrogen(BUN),serum cystatin-C(Cys-C),retinol-binding protein(RBP),β2-MG were detected in the blood biochemistry automatic analyzer. These laboratory markers were inspected before treatment and at the 4th,8th and 12th week after treatment. Results Ninety-six patients in the experiment group and 95 patients in the control group were effectively included in the end. Before treatment,there were no statistic significant differences in urine mALB,mALB/UCr,β2-MG,α1-MG and blood ET-1,NO,TXB2, 6-keto-PGF1α between two groups(all P>0.05). Along with the prolongation of treatment,urine mALB,mALB/UCr,β2-MG,α1-MG and ET-1,TXB2 were significantly reduced,while NO,6-keto-PGF1α were significantly raised in the two groups after treatment,and the above changes in the experimental group were more obvious. There were statistic significant differences of mALB,mALB/UCr,β2-MG,α1-MG and TXB2,6-keto-PGF1αbetween two groups at the 12th week after treatment〔mALB(mg/L):36.6±9.2 vs. 78.6±16.5,mALB/UCr(mg/mmol):3.90±1.97 vs. 9.70±2.90,β2-MG(mg/L):0.25±0.10 vs. 0.40±0.12,α1-MG(mg/L):8.40±2.26 vs. 12.50±3.21,TXB2 (ng/L):75.8±18.7 vs. 94.7±21.7,6-keto-PGF1α(ng/L):73.4±15.2 vs. 65.2±11.5,P<0.05 or P<0.01〕. But there were no statistic significant differences of ET-1 and NO between experimental group and control group at the same time-points〔ET-1(ng/L):57.6±6.9 vs. 59.1±6.2,NO(μmol/L):68.9±11.6 vs. 65.4±10.7,both P>0.05〕. In each of the two groups,the comparisons of the levels of SCr,BUN before and after treatment,there was no statistical significant difference at any time point;the same comparisons between the two groups,there was also no statistic significant difference before treatment and at each of the same time-point after treatment(all P>0.05). The levels of Cys-C,RBP andβ2-MG of the control group after treatment had the tendency of decreasing,but no statistic significant differences were found(all P>0.05). The levels of Cys-C,RBP,β2-MG of the experimental group at the 12th week after treatment were significantly lower than those before treatment〔Cys-C(mg/L):0.72±0.07 vs. 0.89±0.12,RBP (mg/L):53.0±14.2 vs. 66.1±16.5,β2-MG(mg/L):1.86±0.71 vs. 2.79±0.82,all P<0.05〕. Conclusions Qizhi Jiangtang capsule can significantly reduce the levels of urine mALB and mALB/UCr of patients with stageⅢDN and stabilize their renal functions;its therapeutic effect is better then that of valsartan. Its mechanisms are related to the reduction of ET-1,elevation of NO,maintenance of dynamic equilibrium of thromboxane A2/prostacycline(TXA2/PGI2) and protection of vascular endothelial cells.