Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

重组人酸性成纤维细胞生长因子在鼻腔泪囊吻合术中的应用

目的 探讨重组人酸性成纤维细胞生长因子在鼻腔泪囊吻合术中的应用。方法 对2016年3月~2021年12月46例慢性泪囊炎患者,行碘普罗胺泪囊造影,确定阻塞部位位于泪囊。选取手术治疗的慢性泪囊炎患者,随机分为两组,A组患者行经鼻内镜鼻腔泪囊吻合术联合应用重组人酸性成纤维细胞生长因子,B组患者经鼻内镜鼻腔泪囊吻合术,比较两组术后的临床疗效。结果 两组鼻腔泪囊吻合术的患者,经过术后2周、1个月、3个月、6个月对患者进行随访观察,发现A组患者在术后2周和1个月内吻合口周围痂皮较少,吻合口上皮化程度较快,在术后3个月和6个月吻合口无明显差异。结论 重组人酸性成纤维细胞生长因子在创面早期可促进肉芽组织生长,诱导毛细血管胚芽形成与再上皮化,加速鼻腔泪囊吻合口的上皮化的进程。

ACIDIC FIBROBLAST GROWTH FACTOR REDUCES RAT SKELETAL MUSCLE DAMAGE CAUSED BY ISCHEMIA AND REPERFUSION

Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad spectrum mitogenic and non mitogenic activities of FGFs inspired us to study its protecting effects on tissue injuries in ischemia reperfusion condition. We found that systemic administration of aFGF after reperfusion onset prevented severe skeletal muscle injuries. In rats treated with aKGF, the tissue edema was reduced significantly, the tissue viability was increased, and the muscle fibers contained more succinate dehydrogenase (SDH) and adenosine triphosphatasc (ATPase). The pathological results supported the concept of improved prevention with aFGF treatment. The possible tissue protection by aFGF may come from its ability to regulate the concentration of evtra- and intracellular calcium ion. Besides, it may moderate other Ca2+ dependent enzyme conversion processes. Also, it may take part in the vascular tone regulation under ischemia and reperfusion conditions. These results suggest further study of tissue ischemia prevention with FGF and its possible mechanisms in the future.

Observation on Curative Effect of Self-made Wubeizi Decoction Combined with rhaFGF in Promoting Postoperative Wound Healing in Patients with Anal Fistula

[Objectives]To explore the curative effect of Self-made Wubeizi Decoction combined with recombinant human acidic fibroblast growth factor(rhaFGF)in promoting postoperative wound healing in patients with anal fistula.[Methods]A total of 82 patients with anal fistula who underwent anal fistula resection+use of setons in Luodian Hospital during January and March of 2020 were randomly divided into observation group and control group with 41 cases in each group.The control group was given rhaFGF external application regimen,and the observation group was treated with Self-made Wubeizi Decoction on the basis of the control group.After 3 weeks of treatment,the differences in curative effects of TCM syndromes were compared between the two groups.Besides,the changes in TCM symptom scores,inflammatory mediators[interleukin-12(IL-12),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)],anorectal functions[anal resting pressure(ARP),maximal systolic pressure(MSP)and maximum tolerated volume(MTV)of the anal canal],quality of life[GQOLI-74 scores]were compared.[Results]After 3 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group(P<0.05);the levels of TCM symptom scores,IL-12,TNF-α,IFN-γ,ARP,MSP,and MTV in both groups were significantly lower than those before treatment,and these levels in the observation group was significantly lower than that in the control group at the same time(P<0.05).The GQOLI-74 scores of both groups were significantly higher than those before treatment,and the observation group was significantly higher than the control group(P<0.05).[Conclusions]The Self-made Wubeizi Decoction combined with rhaFGF therapy has a significant effect in promoting postoperative wound healing in patients with anal fistula.It can effectively inhibit the local inflammation of patients,facilitate the recovery of anorectal function and improve the quality of life,thus has high clinical application value.