Therapeutic Effects of SRT2104 on Lung Injury in Rats with Emphysema via Reduction of Type II Alveolar Epithelial Cell Senescence

Figures & data

Table 1. Lung function examination in rats from each group.

Group	PR (cm/mL/s)	Cdyn (mL/cm)	PEF (mL/s)
A	0.127 ± 0.046	0.303 ± 0.042	13.876 ± 1.702
B	0.322 ± 0.029*	0.183 ± 0.029*	6.483 ± 1.558*
C	0.261 ± 0.032*^,#	0.201 ± 0.035*^,#	10.010 ± 2.871*^,#

Abbreviations: PR, pulmonary resistance; C_dyn, pulmonary dynamic compliance; PEF, peak expiratory flow.

Values are presented as mean ± SD (n = 15).

* p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 1. Histopathologic changes of lung tissues from control group (A), emphysema group (B), and emphysema + SRT2104 group (C). Sections were stained with hematoxylin and eosin. Magnification, ×200.

Table 2. Quantitative analyses of lung histomorphology in rats from each group.

Group	MLI (μm)	MAA (μm^2)
A	60.24 ± 8.15	4870.24 ± 211.59
B	117.21 ± 13.02*	13781.23 ± 981.28*
C	85.45 ± 7.54*^,^#	10482.76 ± 193.34*^,#

Abbreviations: MLI, mean linear intercept; MAA, mean alveolar airspace.

Values are presented as mean ± SD (n = 15).

* p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 2. SPA and SPC mRNA expression in lung tissues. All analyses were performed in triplicate. The relative expression of SPA and SPC mRNA was calculated with the 2^−ΔΔCt method. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 3. Western blotting analysis of the expression of SPA and SPC in lung tissues. β-actin was provided as the loading control. The expression of protein was analyzed by densitometry and normalized with β-actin. All analyses were performed in triplicate. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 4. Immunohistochemical analysis of the expression of SPA in lung parenchyma from control group (A), emphysema group (B), and emphysema + SRT2104 group (C). The arrows indicate the SPA positive cells. Magnification, ×400. (D) The percentage of SPA positive cells in each group. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 5. Immunohistochemical analysis of the expression of SPC in lung parenchyma from control group (A), emphysema group (B), and emphysema + SRT2104 group (C). The arrows indicate the SPC positive cells. Magnification, ×400. (D) The percentage of SPC positive cells in each group. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 6. SA-β-gal activity of lung tissues from control group (A), emphysema group (B), and emphysema + SRT2104 group (C). The cells in lung samples with blue color were considered SA-β-gal positive, which means senescent cells. The arrows indicate the SA-β-gal-positive cells. Magnification, ×200.

Figure 7. Western blotting analysis of the expression of SIRT1, FoxO3a, p53, and p21 in lung tissues. β-actin was provided as the loading control. The expression of protein was analyzed by densitometry and normalized with β-actin. All analyses were performed in triplicate. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.

Figure 8. SIRT1 deacetylase activity of lung tissues from control group (A), emphysema group (B), and emphysema + SRT2104 group (C). All analyses were performed in triplicate. Values are presented as mean ± SD (n = 15). *p < 0.05 vs. group A; #p < 0.05 vs. group B.