TNF-α and IL-1β Promote Renal Podocyte Injury in T2DM Rats by Decreasing Glomerular VEGF/eNOS Expression Levels and Altering Hemodynamic Parameters

Figures & data

Figure 1 Establishment of an HFD/STZ-induced DN rat model.

Abbreviations: CTL, normal control; DN, diabetic nephropathy; HFD, high-fat diet; IRI, insulin resistance index; STZ, streptozotocin; DM, diabetes mellitus; T2DM, type 2 diabetes mellitus; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; eNOS, endothelial nitric oxide synthases; VEGF, vascular endothelial growth factor; WT-1, Wilms’ tumor-1; SCr, serum creatinine; BUN, blood urea nitrogen; 24h-UP, 24 h urinary total protein; CrCl, estimated creatinine clearance.

Figure 2 Continued.

Figure 2 Biological parameters of the CTL group and the DN group at the different experimental weeks. (A) BW. (B) KW. (C) RI. (D) FINS. (E) FBG. (F) IRI. (G) RBG. (H) TG. (I) TC. (J) SCr. (K) BUN. (L) 24h-UP. (M) UCr. (N) CrCl. Data were presented as mean ± SD. *P < 0.05, vs the CTL group at the same week.

Abbreviations: CTL, normal control; DN, diabetic nephropathy; BW, body weight; KW, kidney weight; RI, renal index; FINS, fasting insulin; FBG, fasting blood glucose; IRI, insulin resistance index; RBG, random blood glucose; TG, triglyceride; TC, total cholesterol; SCr, serum creatinine; BUN, blood urea nitrogen; 24h-UP, 24 h urinary protein; UCr, urea creatinine; CrCl, creatinine clearance.

Figure 3 Comparison of TNF-α and IL-1β levels in serum and kidney tissue. (A) TNF-α levels in serum. (B) IL-1β levels in serum. (C) TNF-α levels in kidney. (D) IL-1β levels in kidney. Data are expressed as the mean ± standard deviation (n=6). *P < 0.05, vs the CTL group at the same week.

Abbreviations: TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; CTL, normal control; DN, diabetic nephropathy.

Figure 4 Continued.

Figure 4 Evaluation of renal hemodynamics of left kidney by color Doppler spectrum ultrasound. (A) Schematic diagram of main artery, segmental artery and interlobar artery. (B) The main artery of the CTL group. (C) The main artery of the DN group. (D) The segmental artery of the CTL group. (E) The segmental artery of the DN group. (F) The interlobar artery of the CTL group. (G) The interlobar artery of the DN group. (H) Comparison of PSV, MV and EDV in the two groups. (I) Comparison of RI and PI in the two groups. All data were obtained from left kidney of rats. Data are expressed as the mean ± standard deviation (n=6). *P < 0.05, comparison in the main artery of the CTL group and the DN group. ^#P < 0.05, comparison in the interlobar artery of the CTL group and the DN group.

Abbreviations: CTL, normal control; DN, diabetic nephropathy; PSV, peak systolic velocity; MV, mean velocity; EDV, end-diastolic velocity; RI, resistive index; PI, pulsation index.

Figure 5 Histological results with light microscopy (×400). (A) Glomerulus of the CTL group. (B) Glomerulus of the DN group. (C) Comparison of the glomerular diameter. (D) Comparison of the relative area of mesangial. All data were obtained from left kidney of rats. Data are expressed as the mean ± standard deviation (n=6). *P < 0.05, vs the CTL group.

Abbreviations: CTL, normal control; DN, diabetic nephropathy.

Figure 6 Comparison of Nephrin, WT-1, TNF-α, IL-1β, eNOS and VEGF mRNA expression levels of kidney. (A) Nephrin expressions. (B) WT-1 expressions. (C) TNF-α expressions. (D) IL-1β expressions. (E) eNOS expressions. (F) VEGF expressions. Data are expressed as the mean ± standard deviation (n=6). *P < 0.05, vs the CTL group.

Abbreviations: CTL, normal control; DN, diabetic nephropathy; WT-1, Wilms’ tumor-1; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; eNOS, endothelial nitric oxide synthases; VEGF, vascular endothelial growth factor.

Figure 7 Comparison of Nephrin, WT-1, TNF-α, IL-1β, eNOS and VEGF protein expression levels of kidney. (A) Nephrin and WT-1 expressions. (B) TNF-α expressions. (C) IL-1β expressions. (D) eNOS and VEGF expressions. Data are expressed as the mean ± standard deviation (n=6). *P < 0.05, vs the CTL group.

Abbreviations: CTL, normal control; DN, diabetic nephropathy; WT-1, Wilms’ tumor-1; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; eNOS, endothelial nitric oxide synthases; VEGF, vascular endothelial growth factor.