Abstract
Background
Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model.
Methods
Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin–eosin and Masson staining. The expressions of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry.
Results
The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-β1, CTGF, and α-SMA significantly reduced in the rosuvastatin group.
Conclusions
The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-β1.
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Acknowledgements
The authors thank Dr Lin Lin, Dr Guoxin Zhang, Dr Xinmin Si, Dr Qiong Wang, and Dr Huaiming Sang for advice and assistance. This study was supported by the National Natural Science Foundation of China (Research Grant # 81800478, # 81900237) and the Natural Science Foundation of Jiangsu Province (Research Grant # BK20181082, # BK20191093). The funders had no role in study design, data collection and analysis, decision to publish, or in the preparation of the manuscript.
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YG and BZ contributed to the study conception and design. BZ, BS, YW, WZ, ML, and YG performed the experiments. Data acquisition and analysis were performed by BZ, BS, YW, MB, WC, and YG. Histopathological injury was scored by MB. The first draft of the manuscript was written by YG and BZ, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All animal experimental protocols were approved by the Institutional Animal and Use Committee of Nanjing Medical University. All institutional and national guidelines for the care and use of laboratory animals were followed.
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Boqian Zhu, Bingzhan Song, Yanjuan Wang, Meiling Bao, Wenfang Cheng, Weifeng Zhang, Meihong Liu, and Yaoyao Gong declare that they have no conflict of interest.
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Zhu, B., Song, B., Wang, Y. et al. Protective effect of rosuvastatin against the formation of benign esophageal stricture. Esophagus 19, 343–350 (2022). https://doi.org/10.1007/s10388-021-00895-1
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DOI: https://doi.org/10.1007/s10388-021-00895-1