1.Probing the anti-rheumatoid arthritis synovial neovascularization of alcoholic extracts of the Miao medicinal plant helleborus thibetanus franchon in rats based on the VEGF/VEGFR2 signaling pathway
Lei HOU ; Yunmei ZHOU ; Dong DING ; Zizhen LI ; Zhigang ZHU ; Wenting SHAN ; Xia LIU ; Fei AI
Acta Laboratorium Animalis Scientia Sinica 2024;32(10):1233-1242
Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P<0.01),increased foot swelling(P<0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P<0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P<0.05);reduction in foot swelling(P<0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P<0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.
2.Urethra rerouted under corpora cavernosus anastomotic urethroplasty for treatment of complex posterior urethral strictures
Yuemin XU ; Qingbing ZHANG ; Zizhen HOU ; Mingjun DU ; Xiangli YANG ; Chao LI ; Lujie SONG ; Hong XIE ; Hongbin LI ; Tao LIANG ; Kaile ZHANG ; Zhenghao DAI ; Qiang FU
Chinese Journal of Urology 2020;41(11):825-829
Objective:To explore the outcomes of urethra around corpora cavernosus anastomotic urethroplasty for the treatment of complex posterior urethral strictures.Methods:Between June 2008 and June 2020, 35 patients with complex posterior urethral strictures were treated using urethra rerouted under one corpora cavernosus anastomotic urethroplasty. The patients’ age was 3-54 years(mean 23.2 years), the urethral stricture or loss length was 4-7 cm(mean 5.2 cm), and 6 patients associated with urethrorectal fistula. The technique involved: ①The anterior urethra is dissected long more than 5 cm, separation of the proximal corporeal bodies, inferior pubectomy and the dissected proximal urethra.②A channel around the left crus of the penis through the inferior pubectomy is separated and urethra rerouted under left corpora cavernosus to allow a tension-free anastomosis to the proximal urethra.Results:Two patients lost follow-up; the remainder 33 patients were followed-up for 3 to 144 months(mean 37 months). Thirty-two patients could void normally(97%), The examination of maximal urinary flow rates(Q max) were taken in 21 patients, of whom Q max was 13.6-35.5 ml/s (mean 17.5 ml/s) in 7 children and 16.3-77.6 ml/s(mean 27.9 ml/s) in 14 adult patients. All 6 patients associated with urethrorectal fistula successful repaired, of these patients 1 had died of hemorrhage of brain 6 years postop. One patient developed urethral stenosis postoperatively. Continence was achieved in 29 patients, the remaining 3 patients had incontinence from mild to moderate. Conclusions:Urethra rerouted under left corpora cavernosus anastomotic urethroplasty is not only an effective surgical salvage option, with low recurrent rate for patients with complex posterior urethral strictures, but also do not cause curve and affect growth of corpora cavernosus.