关键词: 玉夏胶囊, 自发性高血压大鼠, 肾纤维化, TGFβ1, P38/MAPK, ERK/MAPK, MMP9/TIMP1

Abstract:

AIM: To investigate the improvement of Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats (SHR) and its possible mechanism. METHODS: WKYs（Wistar-Kyoto rats）were set as normal control group (0.5% CMC-Na, 5 mL/kg). SHRs were randomly divided into SHR model group (0.5% CMC-Na, 5 mL/kg), Yuxia capsule high dose group (0.6 g/kg), middle dose group (0.3 g/kg) and low dose group (0.15 g/kg). Seven rats in each group. According to the above dose, each group of rats were gavaged once daily for 10 weeks. Diastolic blood pressure (DBP) was measured before administration and 2, 4, 6, 8, 10 weeks during the drug administration by non-invasive tail arterial pressure system. Urine was collected before and 3, 5, 8 week after administration and the urine volume was measured. Automatic biochemical analyzer was utilized to measure the contents of serum creatinine (Scr) and blood urea nitrogen (BUN). Immunohistochemistry was used to detect the levels of TGF-β1 positive cells in kidney. Quantitative reverse transcription PCR (RTqPCR) was applied to detect the expression levels of TGFβ1 mRNA. Western blot was adopted to measure the expressions of ERK1/2，p-ERK1/2，P38，p-P38，MMP-9，TIMP-1 proteins in kidney. RESULTS: Yuxia capsule could dose-dependently reduce DBP and the contents of Scr and BUN, increase urine volume. Expressions of TGF-β1，MMP-9，TIMP-1 and phosphorylation of P38 and ERK1/2 protein level in Yuxia capsule group were lower than those in model group（P<0.05, P<0.01）. CONCLUSION: Traditional Chinese medicine Yuxia capsule demonstrats protective effects against renal fibrosis in a dosedependent manner within a certain range in SHR, of which the mechanism may be associated with reducing diastolic blood pressure, promoting urination, inhibiting P38/MAPK, ERK/MAPK signal pathway and the expressions of TGF-β1，MMP-9 and TIMP-1, recovering the ratio of MMP-9/TIMP-1.

Key words: Yuxia capsule, spontaneous hypertensive rats, renal fibrosis, TGF-β1, P38/MAPK, ERK/MAPK, MMP-9/TIMP-1