1.ShenXiankang formula modulates the Emp3/Tgf-β/Smad3 signaling pathway to ameliorate renal fibrosis
Yufang NI ; Luna ZHANG ; Shuhan YAN ; Qianqian LI ; Hongwei SU ; Qiongdan HU ; Qiong ZHANG ; Li WANG ; Jianchun LI
Acta Laboratorium Animalis Scientia Sinica 2025;33(4):501-511
Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.
2.ShenXiankang formula modulates the Emp3/Tgf-β/Smad3 signaling pathway to ameliorate renal fibrosis
Yufang NI ; Luna ZHANG ; Shuhan YAN ; Qianqian LI ; Hongwei SU ; Qiongdan HU ; Qiong ZHANG ; Li WANG ; Jianchun LI
Acta Laboratorium Animalis Scientia Sinica 2025;33(4):501-511
Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.
3.Investigation on the effect of occupational lead exposure on bone mineral density of workers
Luna WANG ; Ming XU ; Yue GAO ; Xing ZHANG ; Hengdong ZHANG ; Yan AN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(10):752-756
Objective:To understand the occupational health status of a lead-acid battery enterprise in Jiangsu Province, to observe the results of blood lead and bone mineral density (BMD) of the workers exposed to occupational lead, and to explore the effect of occupational lead exposure on BMD, so as to provide basis for the prevention and treatment of occupational lead poisoning and osteoporosis.Methods:An occupational health survey was conducted in a lead-acid battery enterprise in Jiangsu Province in January 2019. Basic information and occupational health examination results of 402 persons exposed to occupational lead were collected, and BMD was measured. Spearman rank correlation test was used to analyze the relationship between blood lead and BMD, and logistic regression analysis was used to analyze the influencing factors of BMD.Results:The blood lead level M ( P25, P75) of 402 occupational lead exposure workers was 220.5 (118.0, 307.0) μg/L, 46 workers (11.4%) had blood lead value ≥400 μg/L, and 5 workers (1.2%) ≥600 μg/L. 124 workers (30.8%) had abnormal BMD. The concentrations of lead dust and lead smoke in the workplace were <0.004-0.027 and <0.021-0.045 mg/m 3, respectively. The positions exceeding the standard point were mainly concentrated in the casting and welding group (44.4%, 4/9) of lead smoke positions. There was a statistically significant difference in the overall distribution of blood lead levels among lead exposure workers with different BMD levels, and there was a positive correlation between blood lead and BMD ( P<0.01) . The results of univariate analysis showed that there were statistically significant differences in the distribution of abnormal BMD among workers exposed to different genders, positions and blood lead levels ( P<0.01) . The results of multivariate logistic regression analysis showed that the risk of abnormal BMD in male workers was 5.069 times of that in female worker (95% CI: 2.906-8.840, P<0.01) . Conclusion:Occupational lead exposure personnel have a high blood lead level and a high abnormal BMD rate. Exposure to lead working environment is an influencing factor for the abnormal BMD of workers, so enterprise managers should pay attention to health protection, occupational health monitoring and supervision of working environment of front-line workers.
4.Investigation on the effect of occupational lead exposure on bone mineral density of workers
Luna WANG ; Ming XU ; Yue GAO ; Xing ZHANG ; Hengdong ZHANG ; Yan AN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(10):752-756
Objective:To understand the occupational health status of a lead-acid battery enterprise in Jiangsu Province, to observe the results of blood lead and bone mineral density (BMD) of the workers exposed to occupational lead, and to explore the effect of occupational lead exposure on BMD, so as to provide basis for the prevention and treatment of occupational lead poisoning and osteoporosis.Methods:An occupational health survey was conducted in a lead-acid battery enterprise in Jiangsu Province in January 2019. Basic information and occupational health examination results of 402 persons exposed to occupational lead were collected, and BMD was measured. Spearman rank correlation test was used to analyze the relationship between blood lead and BMD, and logistic regression analysis was used to analyze the influencing factors of BMD.Results:The blood lead level M ( P25, P75) of 402 occupational lead exposure workers was 220.5 (118.0, 307.0) μg/L, 46 workers (11.4%) had blood lead value ≥400 μg/L, and 5 workers (1.2%) ≥600 μg/L. 124 workers (30.8%) had abnormal BMD. The concentrations of lead dust and lead smoke in the workplace were <0.004-0.027 and <0.021-0.045 mg/m 3, respectively. The positions exceeding the standard point were mainly concentrated in the casting and welding group (44.4%, 4/9) of lead smoke positions. There was a statistically significant difference in the overall distribution of blood lead levels among lead exposure workers with different BMD levels, and there was a positive correlation between blood lead and BMD ( P<0.01) . The results of univariate analysis showed that there were statistically significant differences in the distribution of abnormal BMD among workers exposed to different genders, positions and blood lead levels ( P<0.01) . The results of multivariate logistic regression analysis showed that the risk of abnormal BMD in male workers was 5.069 times of that in female worker (95% CI: 2.906-8.840, P<0.01) . Conclusion:Occupational lead exposure personnel have a high blood lead level and a high abnormal BMD rate. Exposure to lead working environment is an influencing factor for the abnormal BMD of workers, so enterprise managers should pay attention to health protection, occupational health monitoring and supervision of working environment of front-line workers.
5.Selection of anesthetic method in setting up the animal model of orthotopic liver transplantation in rats
Yong PENG ; Jianping GONG ; Changan LIU ; Wei WANG ; Luna YAN
Chinese Journal of General Surgery 2001;0(09):-
Objective To investigate the influences of anesthetic meltod on setting up the animal model of orthotopic liver transplantation(OLT) in rats, in order to properly select the anesthetic method. Methods OLT was performed by modified two-cuff technique in Sprague Dawley rats. 100 rats were randomly divided into 5 groups: control group, ether group, ketamine group, chloral hydrate group and pentobarbital group. The anesthetic process, the influences of anesthetic method on physiologic parameters and hepatic function, and the mortality during anhepatic phase of each group were observed. Results The anesthetic process of each anesthetic method was different,ether anesthesia had fewer impacts on physiologic parameters, and the pentobarbital had great hepatotoxicity. High mortality happened in ketamine group, chloral hydrate group and pentobarbital group during anhepatic phase, while no animal died in ether group. Conclusions Each anesthetic method has significant influences on the OLT rat. Ether anesthesia has fewer effects on physiologic parameters and liver function, and has low mortality during anhepatic phase of OLT rats.So it is the best anesthetic method in setting up the animal model of OLT in rats.
6.Study of the effect of recombinant growth hormone on the tumor cell proliferation in the transplantation liver tumor models in rats
Chinese Journal of General Surgery 1993;0(03):-
Objective To study the effect of reconbinant growrh hormone(rGH) on the tumor cell proliferation in the transplantation liver tumor models in rats,to explore the advantages and disadvantages of rGH in the treatment of liver carcinoma.Methods The male weaning rats were used to vaccinate and transgenerate by intraperitoneal injection of abdominal fluid contarning tumor cells from the celiar transplantation tumor rats, the others weaning rats were used to be the solid tumor rats by subcutaneous vaccination with abdominal fluid of tumor cells.The solid tumor were divided into pieces (2 mm?2 mm?3 mm),which were inserted into the liver of the 82 adult male rats to establish the transplantation liver tumor models.and then the models were divided into experimental group and control group randomly.After 3 days,experimental group were given rGH (0.5U/ kg?d)and control group were given via caudal vein NS for 5 days.All the rats were killed in 8d,10d,12d,respectively.The rats, tumors and livers were weighted,the number of hepatocytes,carcinoma cells and mitotic index were measured,the number of 3 H-TdR incorporation in vivo was measured in 8 days after operation. Results There were no significant difference in all the results between the two groups,except the rat's weight of 8days after operation and the tumor weight in different phase.Conclusions The rGH has no significant effect on the proliferation of tumor cell in transplantation liver models in rats.

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