1.STUDY OF THE EFFECT OF DAURICINE ON PLATELET AGGREGATION AND ITS MECHANISM
Yaoxian DING ; Jian ZHOU ; Xueming YE
Chinese Pharmacological Bulletin 1986;0(04):-
The effect of dauricine on platelet aggregation and its mechan-ism have been studied in the patients and in rabbits. Dauricine inhibited platelet aggregation induced by ADP and generation of thromboxane B2 significantly, but had no effect on plasma 6-keto-PGF1a concentrations in the patients. It did not influence the levels of cAMP of platelets and plasma in rabbits. Its property of antipla-telet aggregation may relate to the influence on arachidonic acid metabolism.
2.Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy
Fengyang DUAN ; Chundong SONG ; Dan SONG ; Ying DING ; Xianqing REN ; Xia ZHANG ; Wensheng ZHAI ; Ting GUO ; Yaoxian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):16-23
ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets (TWPT) in the prevention and treatment of kidney injury in diabetic nephropathy (DN) through the nuclear factor of activated T-cells 2(NFAT2)/cyclooxygenase-2(COX-2) pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group (n=8) and an experimental group (n=34) after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin (STZ) following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated, the remaining 24 model rats were randomly divided into model group, valsartan (8.33 mg·kg-1·d-1) group, and TWPT (5 mg·kg-1·d-1) group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks, body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta, and then the rats were sacrificed for sampling. Biochemical indicators, such as serum blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), blood lipid, blood glucose, and 24-hour urine total protein (24 h UTP), were determined. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay (ELISA) was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)were adopted to detect NFAT2, COX-2 protein and mRNA expression in kidney tissues, respectively. ResultCompared with the normal group, the model group showed elevated 24 h UTP, BUN, SCr, CHO, TG, and FBG, increased serum NFAT2 and COX-2 production and expression (P<0.01), and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). In addition, the pathology of the kidney showed enlarged glomeruli, mild proliferation of mesangial cells, and widened mesangial stroma. Compared with the model group, the TWPT group showed decreased 24 h UTP, BUN, SCr, CHO, TG, and FBG (P<0.05,P<0.01), basically normal glomerular morphology, decreased expression of serum NFAT2 and COX-2 (P<0.01), and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). ConclusionTWPT can alleviate 24 h UTP in DN model rats, protect renal function, and improve renal pathology, and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
3.Effect of Yiqi Yangyin Huoxue Prescription on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway in Diabetic Kidney Disease Rats
Pingping JIA ; Chundong SONG ; Fengyang DUAN ; Ningli WANG ; Ying DING ; Yaoxian WANG ; Xianqing REN ; Wensheng ZHAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):75-81
ObjectiveTo explore the possible mechanism of Yiqi Yangyin Huoxue prescription in the prevention and treatment of kidney injury of diabetic kidney disease(DKD)rats based on NOD-like receptor protein 3(NLRP3)/cysteine protease-1(Caspase-1)/gasdermin D (GSDMD)pyroptosis pathway. MethodFifty male SD rats were randomly divided into normal group (n=8) and modeling group (n=42). The modeling group was given a one-time intraperitoneal injection of streptozotocin (STZ) after high-sugar and high-fat diet for 6 weeks to induce the establishment of a DKD rat model. After successful modeling, the rats were randomly divided into model group, valsartan group (8.33 mg·kg-1), and Yiqi Yangyin Huoxue prescription low-dose and high-dose group (11,22 g·kg-1). After continuous gavage for 6 weeks, the fasting blood glucose (FBG), total cholesterol (CHO), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein quantification (24 h-UTP) were detected in each group of rats. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of kidney tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels. The protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue of rats in each group were determined by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the conditions in normal group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in model group were increased (P<0.01), and the kidney tissue lesions were severe. Compared with the conditions in model group, the levels of FBG, CHO, TG, BUN, SCr, 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in each intervention group were decreased (P<0.05, P<0.01), and the degree of kidney tissue lesions was improved, with Yiqi Yangyin Huoxue prescription high-dose group showing the optimal effect. ConclusionYiqi Yangyin Huoxue prescription could inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway, and thus relieve the inflammatory response of DKD rats and alleviate the pathological damage of the kidneys.