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2022, Vol. 26 ›› Issue (11): 1741-1746Effects of minimally invasive surgery combined with metformin on inflammatory responses in rabbits with intracerebral hemorrhageXu Lin1, Qi Hongshun2, Ge Rucun1, Li Peipei1, Zhen Lixiao1, Feng Xiaoya2
Abstract: BACKGROUND: Our preliminary results have shown that minimally invasive surgery combined with metformin can reduce secondary damage after cerebral hemorrhage and improve the prognosis. However the specific mechanism is still unclear. OBJECTIVE: To observe the effect of minimally invasive surgery combined with metformin on the inflammatory responses of brain tissue around hematoma in a rabbit model of intracerebral hemorrhage, and to explore its specific mechanism. METHODS: Forty-eight male New Zealand rabbits were randomly divided into sham operation group (sham group), intracerebral hemorrhage group (ICH group), minimally invasive surgery group (MIS group), and minimally invasive surgery combined with metformin treatment group (MIS+MET group). Animal models of intracerebral hemorrhage were established using Sawyer’s method in the latter three groups. Pseudohematoma removal surgery was performed in the ICH group, and minimal invasive surgery was performed in the MIS group and MIS+MET group 6 hours after successful modeling. Metformin (50 mg/kg) was administered by gavage to the rabbits in the MIS+MET group once a day for 3 continuous days, and the rabbits in the MIS and ICH groups were given the same amount of normal saline. Neurological deficit (Purdy) score was performed 3 days after treatment. The content of brain water and Evans blue were detected. The expression of tumor necrosis factor-α and interleukin-1β in serum was detected by ELISA. The expressions of Toll-like receptor 4, matrix metalloproteinase 9 and nuclear factor κB proteins in brain tissue were detected by immunohistochemistry and western blot. An ethical approval was obtained from the Experimental Animal Ethics Committee of Shandong Provincial Third Hospital (approval No. DWKYLL-2017001). RESULTS AND CONCLUSION: Compared with the ICH group, Purdy score, brain water content and Evans blue content were significantly decreased in the MIS group and MIS+Met group (P < 0.05), the expression levels of tumor necrosis factor-α and interleukin-1β in serum were decreased (P < 0.05), and the expression of Toll-like receptor 4, matrix metalloproteinase 9 and nuclear factor κB proteins in brain tissue were significantly decreased (P < 0.05). The above indexes were decreased more obviously in the MIS+MET group. These findings indicate that minimally invasive surgery combined with metformin could reduce the inflammatory response and improve the neurological function of rabbits with intracerebral hemorrhage by inhibiting Toll-like receptor 4/nuclear factor κB signaling pathway. Key words:minimally invasive surgery, metformin, intracerebral hemorrhage, inflammatory response, Toll-like receptor 4, nuclear factor κB |