1.Treatment of IgA Nephropathy by Tonifying Kidney and Invigorating Spleen as Well as Detoxifying and Relieving Sore-throat Based on PIgR-CR1-mediated Mucosal-renal Axis
Fan LI ; Hongan WANG ; He NAN ; Mingyu HE ; Chengji CUI ; Yinping WANG ; Yutong LIU ; Shoulin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):237-244
Immunoglobulin A nephropathy (IgAN) is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease (ESRD) in China, which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine (TCM) has certain advantages in treating IgAN. In TCM, IgAN is classified into consumptive disease, hematuria, and edema categories, with the location in the kidney and involving the lung, liver, and spleen. Professor Ren Jixue, a master of TCM, believes that kidney deficiency and spleen deficiency are the root causes of IgAN, and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN, achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections, and polymeric Ig receptor (PIgR) is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria, and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys, causing kidney damage. Complement regulatory protein complement receptor type 1 (CR1) exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells, clearing immune complexes, and inhibiting excessive activation of the complement system. Therefore, regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation, this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.
2.Treatment of IgA Nephropathy by Tonifying Kidney and Invigorating Spleen as Well as Detoxifying and Relieving Sore-throat Based on PIgR-CR1-mediated Mucosal-renal Axis
Fan LI ; Hongan WANG ; He NAN ; Mingyu HE ; Chengji CUI ; Yinping WANG ; Yutong LIU ; Shoulin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):237-244
Immunoglobulin A nephropathy (IgAN) is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease (ESRD) in China, which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine (TCM) has certain advantages in treating IgAN. In TCM, IgAN is classified into consumptive disease, hematuria, and edema categories, with the location in the kidney and involving the lung, liver, and spleen. Professor Ren Jixue, a master of TCM, believes that kidney deficiency and spleen deficiency are the root causes of IgAN, and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN, achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections, and polymeric Ig receptor (PIgR) is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria, and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys, causing kidney damage. Complement regulatory protein complement receptor type 1 (CR1) exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells, clearing immune complexes, and inhibiting excessive activation of the complement system. Therefore, regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation, this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.
3.Occupational stress and its effects on depressive symptoms, anxiety symptoms, and sleep in workers of ferrous and non-ferrous metal mining industry in Gansu Province
Yuhong HE ; Haiya ZHANG ; Nan ZHOU ; Jia XU ; Wenli ZHAO
Journal of Environmental and Occupational Medicine 2025;42(4):444-450
Background Due to the unique working environment and numerous occupational disease hazards, workers in mining industry are particularly susceptible to psychological problems such as occupational stress. Objective To understand the current status of occupational stress, depressive symptoms, anxiety symptoms and sleep quality of workers in ferrous and non-ferrous metal mining industry in Gansu Province, and to explore the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep. Methods From April to December 2022, the workers of 25 large, medium, and small and micro enterprises were selected by stratified cluster random sampling and surveyed in ferrous and non-ferrous metal mining industry in Gansu Province. The Occupational Health Literacy Questionnaire of National Key Population, Core Occupational Stress Scale, Patient Health Questionnaire-q, Generalized Anxiety Disorder, and Self-administer Sleep Questionnaire were used to collect basic information, occupational stress, depressive symptoms, anxiety symptoms, and sleep quality of the workers. Chi-square test was used to compare occupational stress, depressive symptoms, anxiety symptoms and sleep disorders among different categories. Logistic regression model was used to study the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep quality. Results In this study,
4.Exploring Molecular Mechanism of Gypenoside L against Ovarian Cancer Based on Ferroptosis Pathway Mediated by Mature-tRNA-Asp-GTC/ATF3-LPCAT3
Jingxuan ZHU ; Jiao ZHAO ; Qun WANG ; Xiaofei SUN ; Jiaxin WANG ; Hongda ZHANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):107-117
ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer (OC) cells and the regulatory mechanism of gypenoside L (Gyp-L) on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 (CCK-8) assay, and the half-maximal inhibitory concentration (IC50) values of cisplatin (DDP), Gyp-L, and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs (tsRNAs) in the cells after Gyp-L intervention, and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde (MDA), glutathione (GSH), and lipid peroxide (LPO) levels were measured by colorimetry or enzyme linked immunosorbent assay (ELISA) method, Fe2+ content by FerroOrange fluorescent probe, and reactive oxygen species (ROS) content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group, a 50 µmol·L-1 Gyp-L group, and a 100 µmol·L-1 Gyp-L group. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expression of mature-tRNA-Asp-GTC, mature-tRNA-Leu-CAA, mature-mt_tRNA-Tyr-GTA_5_end, mature-tRNA-Val-CAC, mature-mt_tRNA-Glu-TTC, pre-tRNA-Arg-TCT, mature-tRNA-Asn-GTT, hydroxymethylbilane synthase (HMBS), Wnt, β-catenin, glutathione peroxidase 4 (GPX4), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf2), activating transcription factor 3 (ATF3), cystine/glutamate antiporter xCT, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Western blot was performed to detect the expression of HMBS, Wnt, β-catenin, GPX4, KEAP1, Nrf2, ATF3, xCT, LPCAT3, and ALOX15 proteins. ResultsThe 50 µmol·L-1 Gyp-L, 100 µmol·L-1 Gyp-L, DDP, 50 µmol·L-1 Gyp-L+DDP, and 100 µmol·L-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells (P<0.05) and exacerbated cell ferroptosis as reflected by the increase in the content of ROS, MDA, LPO, and Fe2+, as well as a decrease in the content of GSH (P<0.05). Compared with the control group, Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells (P<0.05, |log2Fc|>1). Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention (P<0.05). ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.
5.Exploring Molecular Mechanism of Gypenoside L against Ovarian Cancer Based on Ferroptosis Pathway Mediated by Mature-tRNA-Asp-GTC/ATF3-LPCAT3
Jingxuan ZHU ; Jiao ZHAO ; Qun WANG ; Xiaofei SUN ; Jiaxin WANG ; Hongda ZHANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):107-117
ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer (OC) cells and the regulatory mechanism of gypenoside L (Gyp-L) on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 (CCK-8) assay, and the half-maximal inhibitory concentration (IC50) values of cisplatin (DDP), Gyp-L, and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs (tsRNAs) in the cells after Gyp-L intervention, and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde (MDA), glutathione (GSH), and lipid peroxide (LPO) levels were measured by colorimetry or enzyme linked immunosorbent assay (ELISA) method, Fe2+ content by FerroOrange fluorescent probe, and reactive oxygen species (ROS) content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group, a 50 µmol·L-1 Gyp-L group, and a 100 µmol·L-1 Gyp-L group. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expression of mature-tRNA-Asp-GTC, mature-tRNA-Leu-CAA, mature-mt_tRNA-Tyr-GTA_5_end, mature-tRNA-Val-CAC, mature-mt_tRNA-Glu-TTC, pre-tRNA-Arg-TCT, mature-tRNA-Asn-GTT, hydroxymethylbilane synthase (HMBS), Wnt, β-catenin, glutathione peroxidase 4 (GPX4), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf2), activating transcription factor 3 (ATF3), cystine/glutamate antiporter xCT, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Western blot was performed to detect the expression of HMBS, Wnt, β-catenin, GPX4, KEAP1, Nrf2, ATF3, xCT, LPCAT3, and ALOX15 proteins. ResultsThe 50 µmol·L-1 Gyp-L, 100 µmol·L-1 Gyp-L, DDP, 50 µmol·L-1 Gyp-L+DDP, and 100 µmol·L-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells (P<0.05) and exacerbated cell ferroptosis as reflected by the increase in the content of ROS, MDA, LPO, and Fe2+, as well as a decrease in the content of GSH (P<0.05). Compared with the control group, Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells (P<0.05, |log2Fc|>1). Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention (P<0.05). ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4, pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT, mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT, and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.
6.Research progress of needle-free injection technology
He ZHANG ; Shuo LI ; Yi CHENG ; Zeng-ming WANG ; Nan LIU ; Meng LI ; Hui ZHANG ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2024;59(3):591-599
Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.
7.Analysis on Quality of Sojae Semen Praeparatum Based on Traditional Quality Evaluation
Yihan WANG ; Wangmin LIN ; Shuili ZHANG ; Bing YU ; Tiegui NAN ; Liping KANG ; Guofeng LI ; Xiyuan HE ; Zhilai ZHAN ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):31-42
ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties, the chemical components of Sojae Semen Nigrum(SSN) and Sojae Semen Praeparatum(SSP) were systematically compared and analyzed, and the main fermentation products in different fermentation time were quantitatively analyzed, so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used for the structural identification of the chemical constituents of SSN and SSP, and with the aid of Progenesis QI v2.3 software, the negative ion mode was employed for principal component analysis(PCA) pattern recognition, and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis(OPLS-DA) for two-dimensional data to obtain S-plot, and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC, and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period, and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate(PITC) pre-column derivatization and high performance liquid chromatography(HPLC) gradient elution, and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value(TAV). ResultA total of 19 kinds of differential components were screened out, mainly soybean saponins and isoflavones, and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP, glycoside bond hydrolysis mainly occurred, and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones, the content of flavor substances such as amino acids increased gradually. In the post-fermentation process, protein degradation mainly occurred, after 8 d of post-fermentation, the content of isoflavones was basically stable, while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP, such as the TAV of glutamate is always ahead of other flavor substances, and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation, combined with the traditional evaluation index of "fragrant and strong", it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant, delicious and slightly sweet", and at the same time, the post-fermentation index compounds such as glutamic acid, alanine and valine should be added as the quality control indicators of SSP, so as to standardize the production process and improve the quality of SSP.
8.In vivo and in vitro study on the inhibitory effects and mechanism of aucubin on prostate cancer
Benchun YAN ; Chunyan HE ; Hongwei LI ; Xihao NAN ; Zhihui ZHANG ; Yancheng DI ; He TIAN
China Pharmacy 2024;35(13):1618-1623
OBJECTIVE To investigate the effects of aucubin (AU) on the proliferation and tumor growth of prostate cancer (PC) cells by regulating the protein kinase B (Akt)/murine double minute2 (MDM2)/p53 signaling pathway. METHODS Prostate cancer cell PC3 were separated into control group, 50 μmol/L AU group, 100 μmol/L AU group, SC79 (Akt activator) group (5 μmol/L), and 100 μmol/L AU+SC79 group. The cell cloning and proliferation ability were investigated; the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected. Meanwhile, xenograft tumor models of nude mice were constructed and separated into tumor group, AU group (80 mg/kg), SC79 group (50 mg/kg), and AU+SC79 group (80 mg/kg AU+50 mg/kg SC79), with 10 mice in each group. They were given relevant medicine, once a day, for 21 d. After the last medication, tumor weight was determined, and the expressions of nucleus-associated antigen (Ki-67) and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue. RESULTS In the cell experiment, compared with control group, the cell clonal formation number, proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50 μmol/L AU and 100 μmol/L AU groups were significantly decreased (P<0.05), while the cell apoptosis rate and p53 protein expression levels were significantly increased (P<0.05); however, the change trend of each index in SC79 group was opposite (P<0.05). Compared with 100 μmol/L AU group, the cell clonal formation number, proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100 μmol/L AU+SC79 group were significantly increased (P<0.05), while cell apoptosis rate and p53 protein expression levels were significantly decreased (P<0.05); however, compared with SC79 group, the changing trend of indexes was the opposite (P<0.05). In the in vivo experiment, compared with the tumor group, the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased (P<0.05), and the expression level of p53 protein was significantly increased (P<0.05), but the changing trend of above indexes of nude mice in SC79 group were opposite (P<0.05). Compared with AU group, the tumor mass, Ki-67 positive expression and phosphorylation levels of Akt and MDM2 protein in tumor tissues of nude mice in AU+SC79 group were significantly increased (P<0.05), while the expression level of p53 protein was significantly decreased (P<0.05); however, compared with SC79 group, the changing trend of above indexes was opposite (P<0.05). CONCLUSIONS AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway.
9.In vitro oral simulation evaluation of palatability and chewability of chewable tablets
Aonan ZHONG ; Conghui LI ; Zengming WANG ; Xiaolu HAN ; Hui ZHANG ; Nan LIU ; He ZHANG ; Jintao LIN ; Chunyan LIU ; Aiping ZHENG
China Pharmacy 2024;35(14):1708-1714
OBJECTIVE To evaluate the palatability and chewability of chewable tablets, and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug, the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer, and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets; the rheometer was adopted to measure the viscoelasticity, thixotropy, and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit, principal component content, and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions, and the force required for chewing was within the range of the chewing force of the teeth; chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue, and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing; when chewing with teeth, the internal force of the chewing tablets decreased, causing plastic deformation and crushing. After being crushed, the shape couldn’t be restored, making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.
10.Targeting STAT3 alleviates peritoneal fibrosis by regulating glycolysis and mesothelial-mesenchymal transition
Qilei DENG ; Jiao FU ; Nan LI ; Mengmeng HE ; Dake HUANG ; Pei ZHANG
Acta Universitatis Medicinalis Anhui 2024;59(4):647-653
Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.


Result Analysis
Print
Save
E-mail