1.Mechanisms of Bushen Tongluo Jiangzhuo Prescription in Improving Renal Fibrosis in Rats with Chronic Kidney Disease Based on PI3K/Akt/mTOR Signaling Pathway
Xincui BAO ; Baosheng ZHAO ; Lingling QIN ; Haiyan WANG ; Jing YANG ; You WANG ; Lijia WU ; Yujin LI ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):100-108
ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease (CKD) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsSeventy specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a control group (n=15) and a modeling group (n=55). Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg-1·d-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group, an irbesartan group (20.25 mg·kg-1·d-1), and Bushen Tongluo Jiangzhuo prescription low-, medium-, and high-dose groups (5.82, 11.64, and 23.28 g·kg-1·d-1, respectively), with 10 rats in each group. Each group was administered an equal volume of physiological saline, the corresponding concentration of irbesartan, or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine (SCr), blood urea nitrogen (BUN), urine albumin-to-creatinine ratio (ACR), 24-hour urinary total protein (24 hUTP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry (IHC) was used to detect the expression of PI3K, Akt, phosphorylated Akt (p-Akt), and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K, p-Akt, Akt, phosphorylated mTOR (p-mTOR), and mTOR in renal tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression levels of PI3K, Akt, and mTOR in renal tissues. ResultsCompared with the model group, rats in the irbesartan group and the low-, medium-, and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr, BUN, ACR, 24 hUTP, IL-1β, IL-6, and TNF-α (P<0.01). AST levels were significantly increased (P<0.01), while no significant difference was observed in ALT levels. Histopathological examination revealed that, compared with the model group, renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated, inflammatory cell infiltration was reduced, and interstitial and glomerular fibrosis was markedly improved in all treatment groups, with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K, Akt, and mTOR were significantly downregulated in the high-dose group (P<0.01). IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group (P<0.01). Western blot analysis further confirmed that the expression levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly reduced in the high-dose group (P<0.01). ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats, reduces collagen deposition in renal tissues, and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway, thereby alleviating renal fibrosis.
2.Changes of serum FGF19 and PEDF levels in patients with type 2 diabetic retinopathy
Xueyao GU ; Jun WANG ; Yanxin XIAO ; Xincui ZHAO ; Yaling HAN
Journal of Chinese Physician 2020;22(2):220-223
Objective To observe the expression of FGF19 (fibroblast growth factor 19) and PEDF (pigment epithelium-derived factor) in the serum of type 2 diabetic retinopathy (DR) patients and discuss their significance.Methods Total 89 patients with type 2 diabetes were selected and divided into two groups according to whether they were combined with diabetic retinopathy:45 patients with type 2 diabetes alone (DM group) and 44 patients with type 2 diabetes mellitus combined with retinopathy (DR group).At the same time,40 healthy people were selected as the control group (NDM group).The serum levels of FGF19 and PEDF and their biochemical indexes were detected and compared in each group.The correlation between the indexes and the relationship between FGF19,PEDF and DR were analyzed.Results Compared with NDM group,serum FGF19 level in DM group and DR group decreased,while C-reactive protein (CRP) and PEDF level in DM group and DR group increased (P < 0.05);serum FGF19 level in DR group was lower than that inDMgroup,while serum PEDF level was higher than that in DM group (P <0.05).The levels of fasting blood glucose (FBG),fasting insulin levels (FINS),glycosylated hemoglobin (HbA1c),total cholesterol (TC),high density lipoprotein (HDL) and low density lipoprotein (LDL) in DM and DR groups were higher than those in NDM group (P < 0.05),but there was no significant difference between DM group and DR group (P > 0.05);the levels of Hcy,triacylglycerol (TG) and CRP in DR group were higher than those in DM and NDM group (P < 0.05),and the levels of VLDL were lower than those in DM and NDM group (P < 0.05).The level of serum FGF19 was positively correlated with HDL and CRP in patients with DR (r =0.341,0.623,P < 0.05),and negatively correlated with fasting blood glucose(r =-0.428,P <0.05);The level of serum PEDF in patients with DR were negatively correlated with FINS (r =-0.343,P <0.05).When the serum level of PEDF > 12.76 mg/L,the sensitivity and specificity of PEDF dignosing DR were 80.9% and 56.7% respectively.Conclusions In patients with DR,serum FGF19 level decreased and serum PEDF levels increased.The level of both changes is closely related to DR and may be involved in the development of DR.
3.Analysis of serum fibroblast growth factor 19 and related factors in patients with metabolic syndrome
Yanxin XIAO ; Xincui ZHAO ; Zhiying BIAN ; Dongxun ZHANG ; Jun WANG
Journal of Chinese Physician 2020;22(8):1208-1211
Objective:To investigate the change of fibroblast growth factor 19 (FGF19) in patients with metabolic syndrome (MS) and its diagnostic significance.Methods:According to the number of abnormal metabolic indexes, 175 outpatients and inpatients with MS were divided into Group Ⅲ, Group Ⅳ and Group Ⅴ, with 68 cases, 57 cases and 50 cases, respectively. 40 healthy people were served as normal control group (NC group). Serum FGF19 concentration was measured by enzyme-linked immunosorbent assay (ELISA). The height, weight, waist circumference, blood pressure, blood lipid, fasting and 2-hour postprandial blood glucose, fasting insulin and serum C-reactive protein were measured. Multiple stepwise regression was used to analyze the related influencing factors of FGF19, and the threshold value of FGF19 in the diagnosis of MS was determined by drawing receiver operating characteristic (ROC) curve.Results:The levels of serum FGF19 in NC, Ⅲ, Ⅳ and Ⅴ groups decreased gradually, and the differences were statistically significant ( P<0.05). Multiple stepwise regression analysis showed that BMI, serum total cholesterol, glycosylated hemoglobin and waist circumference were independent influencing factors of FGF19 ( P<0.05). ROC curve analysis showed that the ROC area of FGF19 was 0.849, the threshold was 115.4 pg/ml, with sensitivity 0.875 and specificity 0.667. Conclusions:With the increase of metabolic abnormalities in MS, the level of FGF19 decreased, which was related to obesity and glucose and lipid metabolism disorder. It may be an index to predict and diagnose MS.

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