The final week of drug administration, the eighth, marked the sacrifice of all rats, with subsequent collection of urine, blood, and kidney tissue samples. An examination and observation of IR and podocyte EMT parameters in the DKD model rats was conducted, encompassing general condition, body weight (BW), kidney weight (KW), biochemical parameters and IR indicators, protein expression levels of key signaling and structural molecules in the renal insulin receptor substrate (IRS) 1/phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, foot process morphology and glomerular basement membrane (GBM) thickness, and the expression of key podocyte EMT molecules and structural molecules, alongside glomerular histomorphological characteristics. TFA and ROS treatment regimens were found to positively impact the general condition, biochemical indicators, kidney morphology, and body weight (KW) in DKD model rats. TFA and ROS treatments produced the same ameliorative effects on body weight, urinary albumin-to-creatinine ratio, serum creatinine, triglyceride levels, and KW values. In addition to other improvements, both methods could refine IR indicators; however, ROS proved superior in augmenting fast insulin (FIN) and homeostasis model assessment of insulin resistance (HOMA-IR) compared to TFA. faecal immunochemical test In the third place, they both exhibited the capacity to enhance protein expression levels within the IRS1/PI3K/Akt signaling pathway, resulting in varying degrees of glomerulosclerosis amelioration, with comparable beneficial effects observed. immunoaffinity clean-up Importantly, both methods could lessen podocyte damage and the epithelial-mesenchymal transition (EMT), with TFA exhibiting a more pronounced beneficial effect than ROS. This investigation concluded that, in DKD, IR-induced podocyte EMT and glomerulosclerosis may be directly associated with diminished IRS1/PI3K/Akt pathway activation within the kidney. TFA's suppression of podocyte EMT in DKD, similar to ROS's effects, is plausibly linked to the activation of the IRS1/PI3K/Akt signaling pathway and improved insulin resistance, thus offering a scientific perspective on TFA's action against DKD. This research offers initial pharmacological insight into the efficacy of TFA in addressing diabetic complications.
The study investigated the relationship between Tripterygium wilfordii multi-glycosides (GTW) and renal injury in diabetic kidney disease (DKD) rats, focusing on the pyroptosis pathway via the Nod-like receptor protein 3 (NLRP3)/cysteine-aspartic acid protease-1 (caspase-1)/gasdermin D (GSDMD) pathway and associated mechanisms. For the study, 40 male SD rats were randomly assigned to either a normal group (8 rats) or a model group (32 rats). A high-sugar, high-fat diet, combined with a single intraperitoneal injection of streptozotocin (STZ), was employed to induce diabetic kidney disease (DKD) in rats within the modeling group. Consequent to successful modeling, they were randomly categorized as members of the model group, the valsartan (Diovan) group, or the GTW group. The normal group and the model group were administered normal saline, while the valsartan group received valsartan and the GTW group received GTW over six weeks. Biochemical tests were used to determine the levels of blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), albumin (ALB), and 24-hour urinary total protein (24h-UTP). this website Renal tissue's pathological characteristics were observable through the application of hematoxylin and eosin (H&E) staining. ELISA procedures were used to detect the presence of interleukin-1 (IL-1) and interleukin-18 (IL-18) in serum samples. The expression of pyroptosis pathway-related proteins in renal tissue was analyzed through Western blot, and the expression of the corresponding genes was determined by RT-PCR. The model group's renal function was significantly impaired compared to the normal group, manifesting as elevated BUN, Scr, ALT, and 24-hour urinary total protein (24h-UTP). Further, the model group displayed elevated serum levels of IL-1 and IL-18 (P<0.001), along with decreased serum albumin (P<0.001) and severe pathological kidney damage. Remarkably, high levels of NLRP3, caspase-1, and GSDMD protein and mRNA were observed in the renal tissue (P<0.001). Observing the model group, the valsartan and GTW groups exhibited lower BUN, Scr, ALT, and 24-hour urinary total protein levels. These groups also showed lower serum levels of IL-1 and IL-18 (P<0.001) and higher levels of ALB (P<0.001), alongside a reduction in kidney pathological damage. The renal tissue demonstrated a decrease in NLRP3, caspase-1, and GSDMD protein and mRNA (P<0.001 or P<0.005). By decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, GTW might control pyroptosis, thereby decreasing the inflammatory response and lessening pathological injury to the kidneys of DKD rats.
Diabetes, a chronic metabolic disorder, is marked by the occurrence of diabetic kidney disease, which remains the top cause of end-stage renal disease. The significant pathological features of this condition encompass epithelial mesenchymal transition (EMT) in the glomerulus, podocyte apoptosis and autophagy, and the compromised structure of the glomerular filtration barrier. In physiological contexts, the TGF-/Smad signaling pathway, involved in apoptosis, proliferation, and differentiation, is a target of precise regulation orchestrated by numerous mechanisms. Currently, numerous investigations have revealed the TGF-/Smad signaling pathway to be a pivotal component in the development of diabetic nephropathy. Traditional Chinese medicine, with its complex composition encompassing multiple components, targets, and pathways, exhibits potential benefits in diabetic kidney disease management. The use of traditional Chinese medicine extracts, formulations, and compound prescriptions can help improve renal injury in diabetic kidney disease by regulating the TGF-/Smad signaling pathway. The TGF-/Smad signaling pathway's mechanism in diabetic kidney disease was examined in detail by outlining the link between key targets and disease progression. This study also reviewed recent advances in traditional Chinese medicine's approach to diabetic kidney disease treatment through TGF-/Smad pathway intervention, offering valuable insights for future research and therapeutic strategies.
The interplay of disease and syndrome is a key area of research in contemporary integrated traditional Chinese and Western medicine. Treatment protocols for a disease-syndrome pairing vary based on emphasis. This variation can manifest as diverse treatments for similar diseases, determined by unique syndromes, or single treatments for distinct illnesses, linked by shared syndromes. Alternatively, different treatments might address the same syndrome yet vary based on associated diseases. The mainstream model integrates modern medicine's disease identification with traditional Chinese medicine's syndrome identification and core pathogenesis. However, the current research examining the combination of disease and syndrome, and the fundamental pathogenesis, tends to concentrate on the discrepancies between disease and syndrome presentations, and the distinction between syndromic approaches and treatment strategies. Therefore, the study advocated for the research principle and model of core formulas-syndromes (CFS). The research approach of CFS, rooted in the formula-syndrome correspondence theory, seeks to explore and document core disease pathogenesis by identifying key formulas and syndromes. Research into the diagnostic criteria for the use of formulas, the distribution patterns of these formulas and the syndromes of diseases they treat, the development of medicinal syndromes based on the relationships between formulas and syndromes, the laws governing formula combinations determined by formula-syndrome associations, and the dynamic evolution of formula-syndrome relationships is ongoing. Research into the diagnostic criteria for formulas, drawing upon the insights of ancient texts, clinical case histories, and medical records, as well as leveraging expert opinions, factor analysis, and clustering techniques, aims to unravel diagnostic data concerning ailments, symptoms, observable indicators, and pathophysiological processes. The patterns of formula and syndrome distribution for diseases are frequently established via a combination of literature research and cross-sectional clinical studies, categorizing specific disease types according to formulas and syndromes, while utilizing diagnostic criteria for formula indications. The investigation into the development of medicinal syndromes seeks to elucidate the principles governing medicinal syndromes, drawing upon both literary and clinical research. The core remedies for a disease tend to be combined regularly in prescriptions with other elements. The dynamic evolution of formulas and syndromes, in disease development, represents the continuous alteration and modification of these elements in response to temporal and spatial shifts. The CFS paradigm fosters the merging of disease, syndrome, and treatment approaches, and this strengthens the research model of unified disease and syndrome understanding.
The earliest known record of the Chaihu Jia Longgu Muli Decoction appears in the Treatise on Cold Damage, authored by Zhang Zhong-jing during the Eastern Han dynasty. The medical text at hand describes its original purpose in treating Shaoyang and Yangming syndrome patients. Employing contemporary pathophysiological understanding, this study reinterpreted the time-honored principles of Chaihu Jia Longgu Muli Decoction. The original records describing “chest fullness,” “annoyance,” “shock,” “difficult urination,” “delirium,” and “heavy body and failing to turn over” have a profound pathophysiological origin, impacting the cardiovascular, respiratory, nervous, and mental systems. This formula is broadly used to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases. It also addresses hypertension, arrhythmia, and other cardiovascular diseases, along with insomnia, constipation, anxiety, depression, cardiac neurosis, and various other acute and chronic conditions, encompassing those within psychosomatic medicine.