Objective. To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods. Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results. The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1β, IL-6, IL-18, and TNF-α were increased ( P < 0.05 ); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased ( P < 0.05 ); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1β and IL-6 were reduced ( P < 0.05 ); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased ( P < 0.05 ); and the number of TUNEL-positive cells was decreased. Conclusion. DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.
Chronic kidney disease (CKD) is a major public health issue that is highly prevalent worldwide. Pyroptosis is an important pathological mechanism underlying kidney cell damage in CKD and is associated with the classic caspase-1-mediated pathway and nonclassic caspase-4/5/11-mediated pathway. The NLRP3-caspase-1-GSDMD signaling pathway is the key mechanism of kidney cell pyroptosis in CKD, and noncoding RNAs such as lncRNAs and miRNAs are important regulators of kidney cell pyroptosis in CKD. In addition, the NLRP1/AIM2-caspase-1-GSDMD and caspase-3-GSDME signaling pathways have also been shown to mediate kidney cell pyroptosis. Traditional Chinese medicine (TCM) and extracts can interfere with the occurrence and development of kidney cell pyroptosis in CKD by inhibiting the NLRP3 signaling pathway and oxidative stress, activating Nrf-2 signaling, protecting mitochondrial integrity, regulating AMPK signaling, and regulating TXNIP/NLRP3 axis, which have become increasingly prominent. It is critical to explore the effects of TCM on kidney cell pyroptosis in CKD and its mechanisms to identify targets and develop new and effective drugs.
In view of the problem of how to set up general undergraduate artificial intelligence courses, on the basis of carefully combing and summarizing years of teaching exploration and practice, it is proposed to set Artificial Intelligence (AI) courses in the lower grades of the university. Taking the teaching practice carried out by Liaoning Institute of Science and Engineering as an example, the “12365” principle is proposed based on the CDIO concept, and corresponding teaching reform and practice are carried out.
BackgroundThe main purpose is to establish an ideal arrhythmia model with isoproterenol and explore its mechanism.MethodsFifty healthy male SD rats were randomly divided into the control (CON) group, subcutaneous injection (SC) group(ISO 5 mg/kg for 2 consecutive days), intraperitoneal injection (IP) group (ISO 5 mg/kg for 2 consecutive days), 2+1 group (ISO 5mg/kg by SC for 2 consecutive days, then ISO 3mg /kg by IP for 1 day), 6+1 group ( ISO 5mg/kg by SC for 6 consecutive days, then ISO 3mg /kg by IP for 1 day).The ECG were recorded by BL-420F system. The pathological changes in myocardial tissue were observed by HE and Masson staining. The serum cTnI, TNF-α, IL-6, and IL-1β levels were detected by ELISA. Serum CK, LDH and oxidative stress-related indicators were detected by an automatic biochemical analyser. ResultsThe cardiomyocytes in the CON group rats were normal, while those in the other groups showed signs of disorder, unclear borders, and lysis and necrosis, especially in the 6+1 group. The incidence of arrhythmia, arrhythmia score, and the levels of serum myocardial enzymes, troponin, and some inflammatory factors in the 2+1 group and 6+1 group were higher than those in the single injection way (P<0.01 or P<0.05). The indicators in the 6+1 group were mostly higher than those in the 2+1 group (P<0.01), and the SOD level in the 6+1 group was lower than that in the CON group; the MDA and NO higher(P<0.01 or P<0.05). ConclusionThe combined mode of ISO injection (SC with IP) is more likely to induce arrhythmia than single ISO injection. The "6+1" method of ISO injection can establish a more stable arrhythmia model. Cardiomyocyte damage induced by oxidative stress and inflammation is an important mechanism.
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