Ferulic Acid Alleviates Oxidative Stress-Induced Cardiomyocyte Injury by the Regulation of miR-499-5p/p21 Signal Cascade

Figure 5

Ferulic acid inhibits isoproterenol-induced oxidative stress and cardiomyocyte apoptosis by regulating the miR-499-5p/p21 signaling pathway in vivo. An osmotic pump filled with isoprenaline in saline (30 mg/kg per day) or saline alone was delivered subcutaneously by infusion for 14 days after the operation to insert the pump. Equal volumes of ferulic acid (30 mg/kg/day) or saline were administered to mice daily through oral gavage starting 3 days before the operation and continuing until the end of the experiments. (a), (b) Representative images of mouse hearts and the average heart weight to tibia length ratio (HW/TL) in sham, isoproterenol- (ISO-), isoproterenol + ferulic acid- (ISO + FA-), and ferulic acid- (FA-) treated mice (n = 6). (c) Histological analysis of heart sections by H&E staining in sham-, ISO-, ISO + FA-, and FA-treated mice (n = 6). (d). (e) Images of Sirius Red and quantitative analysis of heart fibrosis of the heart sections of sham-, ISO-, ISO + FA-, and FA-treated mice (n = 6). (f), (g) TUNEL staining and statistical analysis of the TUNEL-positive nucleus rates of heart sections from sham-, ISO-, ISO + FA-, and FA-treated mice (n = 6). (h), (i), (j) Real-time quantitative PCR analysis of miR-499-5p, p21, and Col1a1 mRNA levels in the four groups (n = 6). (k) Western blot and statistical analysis of p21, p-p38, p38, Bcl-2, Bax, and c-caspase-3 in the four groups of mice (n = 6). ^∗, ^∗∗, and ^∗∗∗.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

(j)

(k)

(l)

(m)

(n)

(o)