Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway.
10.19540/j.cnki.cjcmm.20230113.401
- Author:
Chun-Dong SONG
1
;
Dan SONG
2
;
Ping-Ping JIA
1
;
Feng-Yang DUAN
1
;
Ying DING
1
;
Xian-Qing REN
1
;
Wen-Sheng ZHAI
1
;
Yao-Xian WANG
3
;
Shu-Li HUANG
1
Author Information
1. the First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000,China Department of Pediatrics,Henan University of Chinese Medicine Zhengzhou 450000,China.
2. Henan University of Chinese Medicine Zhengzhou 450046,China.
3. Beijing University of Chinese Medicine Beijing 100029,China.
- Publication Type:Journal Article
- Keywords:
NLRP3/caspase-1/GSDMD;
diabetic kidney disease;
multi-glycosides of Tripterygium wilfordii;
pyroptosis
- MeSH:
Rats;
Male;
Animals;
Diabetic Nephropathies/genetics*;
Interleukin-18/metabolism*;
Glycosides/pharmacology*;
Tripterygium;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Rats, Sprague-Dawley;
Caspase 1/metabolism*;
Pyroptosis;
Uridine Triphosphate/pharmacology*;
Kidney;
Valsartan/pharmacology*;
RNA, Messenger/metabolism*;
Diabetes Mellitus
- From:
China Journal of Chinese Materia Medica
2023;48(10):2639-2645
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.
