Mechanism of Astragaloside IV in Treatment of Renal Tubulointerstitial Fibrosis.

Tubulointerstitial fibrosis (TIF) is one of the key indicators in evaluating the renal function of patients. Mild TIF can cause a vicious cycle of renal tubular glomerular injury and aggravate renal disease. Therefore, studying the mechanisms underlying TIF is essential to identify therapeutic targets, thereby protecting the renal function of patients with timely intervention. Astragaloside IV (AS-IV) is a Chinese medicine component that has been shown to inhibit the occurrence and progression of TIF via multiple pathways. Previous studies have reported that AS-IV protected against TIF by inhibiting inflammation, autophagy, endoplasmic reticulum stress, macrophages, and transforming growth factor-ß1, which laid the foundation for the development of a new preventive and therapeutic option for TIF.

[Mechanism of traditional Chinese medicine in regulating NLRP3 inflammasomes to alleviate renal interstitial fibrosis in diabetic nephropathy: a review].

Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.

Mitophagy in renal interstitial fibrosis.

As a high energy consumption organ, kidney relies on a large number of mitochondria to ensure normal physiological activities. Under specific stimulation, mitophagy and mitochondrial dynamics (fission, fusion) cooperatively regulate mitochondrial quality and participate in many life activities such as energy metabolism, inflammatory response, oxidative stress, cell senescence and death. Mitophagy plays a key role in the progression of acute kidney injury and chronic kidney disease. The early induction of oxidative stress in renal parenchyma, the activation of pro-inflammatory cytokines and TGF-ß signal pathway are closely related to renal interstitial fibrosis. Macrophage reprogramming is also considered to be an important participant in the progression of kidney fibrosis. This review summarizes the molecular mechanism of mitochondrial autophagy and its relationship with the pathway of promoting fibrosis, and discusses the possibility of restoring mitophagy balance as a pharmacological target for the treatment of renal interstitial fibrosis, so as to provide new ideas for more efficient anti-fibrosis and delay the progress of chronic kidney disease.

[The role of podocyte autophagy and endoplasmic reticulum stress in diabetic kidney disease].

Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and it has become the leading cause of chronic renal failure in China. Podocytes are highly differentiated epithelial cells and are the important part of the glomerular filtration barrier. Apoptosis and shedding of podocytes, foot process fusion and decreased expression of slit membrane proteins can lead to proteinuria, which in turn affects the progression of DKD. Autophagy is an important process for eukaryotic cells to degrade cytoplasmic proteins and organelles,the increase of autophagy level helps to reduce podocytes damage. Endoplasmic reticulum stress (ERS) is the accumulation of misfolded proteins in cells. It allows the cells into stress state, and may be able to regulate cell damage in both directions. Autophagy and ERS are regulated by multiple signaling pathways and are considered to be closely related to the occurrence and development of DKD. This article explained some pathways and the role of podocyte autophagy and ERS in DKD, and the interaction between podocyte autophagy and ERS, which providing some potential targets for the treatment of DKD by interfering with podocyte autophagy and ERS.

[Treatment of stage 3b diabetic kidney disease patients with macroalbuminuria by qizhi jiangtang capsule: a multicenter randomized control clinical study].

OBJECTIVE: To observe the efficacy and safety of Qizhi Jiangtang Capsule (QJC) in treating stage 3b diabetic kidney disease (DKD) patients with macroalbuminuria. METHODS: Patients who conformed to the diagnostic criteria of stage 3b DKD were randomly assigned to two groups according to random digital table, the experiment group and the control group, 84 in each group. All patients received a two-week elution period, and then were treated with basic Western therapy. Patients in the experiment group took QJC, 5 pills per time, 3 times a day, while those in the control group took Valsartan Capsule 160 mg each time, once daily. The observation period of follow-ups was limited within 6 months, and the time points were set as the baseline, 1st month, 3rd month, and 6th month. Systolic blood pressure (SBP), diastolic blood pressure (DBS), 24 h urine protein quantitative (24 h UPQ), plasma albumin (ALB), and serum creatinine (SCr) were detected and recorded, and estimated glomerular filtration rate (eGFR) was calculated. The occurrence of hypoglycemic reaction, coagulation disorder, gastrointestinal tract reaction, allergy, hyperkalemia, doubling of creatinine, and overall adverse events were observed and recorded at same time. RESULTS: Finally 81 patients in the experiment group and 80 patients in the control group were effectively included. Compared with the baseline level, SBP and DBS obviously decreased in the control group at month 1 of treatment (P < 0.05), and more significantly decreased at month 6 of treatment (P < 0.01). SBP at month 1, 3, and 6 of follow-ups; DBS at month 6 of follow-ups was lower in the control group than in the experiment group (P < 0.05). At month 1, 3, and 6 of follow-ups, 24 h UPQ of the experiment group was significantly lower than the baseline level (P < 0.01). It was also significantly lower than the level of the control group at the same time point (P < 0.05). There was no significant difference in 24 h UPQ at month 1, 3, and 6 of follow-ups between the control group and the baseline level (P > 0.05). ALB of the experiment group showed an increasing trend. It was significantly higher than the baseline level at month 6 (P < 0.05), which was also higher than that of the control group at same period (P < 0.05). There was no significant difference in the ALB level in the control group (P > 0.05). SCr of two groups showed an increasing trend. SCr of the experiment group was significantly higher at month 1, 3, and 6 follow-ups than the baseline level (P < 0.05). But the increment of SCr was higher in the control group than in the experimental group, and obviously higher than the baseline levels (P < 0.05). eGFR of both groups showed a decreasing trend. The decrement was higher in the control group than in the experimental group (P < 0.05). The proportion of progression of renal functions at month 1, 3, and 6 of follow-ups in the experimental group was 0.0% (0 case), 9.55% (8 cases), and 21.4% (18 cases), while they were 8.3% (7 cases), 21.4% (18 cases), and 40.5% (34 cases) in the control group. There was no statistical difference in the proportion of progression of renal functions between the two groups at month 3 and 6 of follow-ups (P < 0.05). There was no statistical difference in the incidence of adverse reactions between two groups (P > 0.05). CONCLUSION: QJC could effectively reduce urinary protein of patients with stage 3b DKD, and delay the progression of renal functions.

[Effect of total saponins of Panax notoginseng on urinary albumin in patients with chronic renal failure].

OBJECTIVE: To observe the curative effect of total saponins of Panax notoginseng (PNS) on chronic renal failure (CRF). METHODS: Sixty patients with CRF (non-uremic) were randomly divided into the experimental and the control groups, with 30 cases in each group. Patients in experimental group were given PNS extract Xueshuantong 0.45 g on the basis of the general symptomatic treatment, once a day. While the patients in the control group were treated with Bailing capsule of 1.0 g, three times a day. Total therapeutic courses were 2 months for both groups. The changes in renal function, hemoglobin, 24-hour urinary protein, parathyroid hormone (PTH), N-acutely-ß-D-glucosaminidase (NAG) were observed in two groups. RESULTS: After 2 months, the changes in serum creatinine (SCr), clearance rate of endogenous creatinine (CCr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin, 24-hour urinary protein were improved in both groups, while the changes in CCr, BUN, hemoglobin, 24-hour urinary protein in the experimental group were more obvious [CCr (ml/s): 0.36±0.13 vs. 0.34±0.12, BUN (mmol/L): 15.66±9.05 vs. 20.32±8.30, hemoglobin (g/L): 101.2±9.4 vs. 95.4±8.7, 24-hour urinary protein (mg): 1 040±450 vs. 2 360±390, all P<0.05]. After treatment, NAG (U/L) were decreased significantly only in control group (18.2±9.8 vs. 28.9±12.0, P<0.05). CONCLUSION: PNS has a good therapeutic effect for the treatment of CRF (non-uremic). It possesses such therapeutic effects as improving the renal function, and lowering urine protein.