1.Single-center experience in the diagnosis and treatment of gastrointestinal bleeding after renal transplantation
Organ Transplantation 2025;16(3):467-473
Objective To analyze the clinical characteristics of patients with gastrointestinal bleeding after renal transplantation and summarize the diagnostic and therapeutic experience. Methods Clinical data of 16 patients with gastrointestinal bleeding after renal transplantation admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to January 2025 were collected, including clinical manifestations, laboratory tests and auxiliary examination results such as gastroscopy and colonoscopy. The bleeding sites, causes, treatment plans and outcomes of the patients were analyzed, and relevant literature was reviewed. Results Among the 16 patients with gastrointestinal bleeding, 12 had upper gastrointestinal bleeding (3 with esophageal bleeding, 7 with gastric bleeding and 2 with duodenal bleeding) and 4 had lower gastrointestinal bleeding (2 with ileal bleeding and 2 with anal bleeding). Among the 16 patients, the 4 with lower gastrointestinal bleeding all presented with hematochezia. Of the 12 with upper gastrointestinal bleeding, 2 patients only had positive fecal occult blood and decreased hemoglobin levels without hematemesis or melena, 9 patients had melena and 1 patient had hematemesis. The hemoglobin levels of the 16 patients were (71±18) g/L. One patient had symptoms of shock, 9 had symptoms of anemia such as dizziness, fatigue and chest tightness, and 6 had good general conditions. Among the 16 patients, 10 had mild gastrointestinal bleeding and stable general conditions, which were curable by drugs. Two patients with peptic ulcers and exposed vessels on gastroscopy were treated with hemostasis by titanium clips. One patient with gastroesophageal tear was treated with hemostasis by titanium clips. One patient with esophageal variceal rupture bleeding was treated with endoscopic variceal ligation. One patient with hemorrhoidal bleeding underwent selective annual resection of the superior hemorrhoidal mucosa with stapled hemorrhoidopexy. One patient with active ileal bleeding on emergency enhanced abdominal CT was treated with endovascular embolization of the mesenteric artery. One patient was discharged automatically due to coma caused by extensive cerebral infarction, and the remaining patients were all cured and discharged with good prognosis. Conclusions Gastrointestinal bleeding after renal transplantation has diverse clinical manifestations, varying severity and many causes. Early diagnosis and treatment should be actively carried out. In addition to drug therapy, endoscopic, interventional or surgical treatment may be used when necessary to improve the diagnostic and therapeutic effects and minimize the functional damage of gastrointestinal bleeding to the transplant kidney.
2.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
3.Zhenzhu Tiaozhi Capsules Reduce Renal Lipid Deposition and Inflammation in Mouse Model of Diabetic Kidney Disease via SCAP-SREBP-1c/NLRP3 Signaling Pathway
Tao ZHANG ; Jie TAO ; Yinghui ZHANG ; Yiqi YANG ; Xianglu RONG ; Jiao GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):114-121
ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin (STZ) at 40 mg·kg-1 for 5 days combined with a high-fat diet (HFD). Fasting blood glucose (FBG) ≥ 11.1 mmol·L-1, increased urine volume, and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows: Blank, model, low- and high-dose (0.98 and 1.96 g·kg-1, respectively) Zhenzhu Tiaozhi capsules, and losartan potassium (30 mg·kg-1), with six mice in each group. After 12 weeks of continuous gavage, urine and kidney specimens were collected, and the 24-h urinary protein and the urinary albumin-to-creatinine ratio (UACR) in mice were measured. Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c), and NOD-like receptor protein 3 (NLRP3) in the renal tissue. ResultsCompared with the blank group, the model group showed increases in 24-h urinary protein and UACR (P<0.05), glomeruli exhibiting capsule adhesion, collagen fiber deposition, mesangial proliferation, and inflammatory cell infiltration, elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), reduced positive expression of nephrin (P<0.05), increased lipid deposition (P<0.05), and up-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. Compared with the model group, the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR (P<0.05), and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein (P<0.05). Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated, with reduced inflammatory infiltration, collagen fiber deposition, and mesangial proliferation, and increased positive expression of nephrin in the renal tissue (P<0.05). In addition, all the treatment groups showed reduced lipid droplets (P<0.05), lowered levels of IL-1β, IL-6, and TNF-α (P<0.05), and down-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway, which reduces renal lipid deposition and inflammation.
4.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
5.Zhenzhu Tiaozhi Capsules Reduce Renal Lipid Deposition and Inflammation in Mouse Model of Diabetic Kidney Disease via SCAP-SREBP-1c/NLRP3 Signaling Pathway
Tao ZHANG ; Jie TAO ; Yinghui ZHANG ; Yiqi YANG ; Xianglu RONG ; Jiao GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):114-121
ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin (STZ) at 40 mg·kg-1 for 5 days combined with a high-fat diet (HFD). Fasting blood glucose (FBG) ≥ 11.1 mmol·L-1, increased urine volume, and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows: Blank, model, low- and high-dose (0.98 and 1.96 g·kg-1, respectively) Zhenzhu Tiaozhi capsules, and losartan potassium (30 mg·kg-1), with six mice in each group. After 12 weeks of continuous gavage, urine and kidney specimens were collected, and the 24-h urinary protein and the urinary albumin-to-creatinine ratio (UACR) in mice were measured. Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c), and NOD-like receptor protein 3 (NLRP3) in the renal tissue. ResultsCompared with the blank group, the model group showed increases in 24-h urinary protein and UACR (P<0.05), glomeruli exhibiting capsule adhesion, collagen fiber deposition, mesangial proliferation, and inflammatory cell infiltration, elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), reduced positive expression of nephrin (P<0.05), increased lipid deposition (P<0.05), and up-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. Compared with the model group, the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR (P<0.05), and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein (P<0.05). Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated, with reduced inflammatory infiltration, collagen fiber deposition, and mesangial proliferation, and increased positive expression of nephrin in the renal tissue (P<0.05). In addition, all the treatment groups showed reduced lipid droplets (P<0.05), lowered levels of IL-1β, IL-6, and TNF-α (P<0.05), and down-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway, which reduces renal lipid deposition and inflammation.
6.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
7.Correlation of sleep problems with emotional and behavioral problems among children with cerebral palsy
YANG Jiewen, HUANG Shaoyi, HUANG Shan, DENG Haorong, KANG Tao, CHEN Yajun
Chinese Journal of School Health 2025;46(2):181-185
Objective:
To investigate the correlation of emotional and behavioral problems with sleep problems in children with cerebral palsy, so as to provide reference for intervention of emotional and behavioral problems in children.
Methods:
A cross sectional survey was conducted, and 402 children aged 6-18 with cerebral palsy who were adopted by social welfare institutions in Guangzhou City from January 2023 to January 2024 were selected to investigate their full time nurses. The Parents Strengths and Difficulties Questionnaire (SDQ) was used to assess the emotional and behavioral problems of children with cerebral palsy, and the Children s Sleep Habits Questionnaire (CSHQ) was used to assess sleep problems. Multiple linear regression analysis was used to analyze the correlation between the sleep problem of children with cerebral palsy and the emotional and behavioral problems.
Results:
The prevalence of emotional and behavioral difficulties among children with cerebral palsy was 15.7%. The median sleep problem score of children with emotional and behavioral problems [37.0(36.0, 41.0)] was significantly higher than that of children without emotional and behavioral [35.0(34.0, 36.0)] ( Z =-5.74, P <0.01). The results of multiple linear regression analysis showed that after adjusting covariables such as age, gender, cerebral palsy classification, language retardation, visual impairment and epilepsy, the total sleep problem score of children with cerebral palsy was positively correlated with the total difficulty score ( β= 0.28, 95%CI =0.17-0.34, P <0.05).
Conclusions
Sleep problems in children with cerebral palsy are associated with emotional and behavioral difficulties. Understanding of the management of sleep problems in children with cerebral palsy should be enhanced to reduce the incidence of emotional and behavioral problems in children with cerebral palsy.
8.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
9.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
10.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.


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