Histopathological insights and therapeutic prospects of MCC950 in diabetes-associated autonomic-related structural alterations in a type 1 diabetes Wistar rat model

Figures

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  Fig. 1. Chemical structure of MCC950 sodium (C20H23N2NaO5S).

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  Fig. 2. The schematic diagram illustrated four groups of rats: a non-diabetic control group, an experimental diabetic positive control group treated with insulin, treated with MCC950, and an untreated diabetic group, with n = 10 in each group

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  Fig. 3. After sacrifice, the gross features of the dissected left stellate ganglion of the Wistar rats were examined. Careful dissection under microscopy aided in identifying nearby landmarks such as the longus colli muscle, 1st and 2nd rib

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  Fig. 4. A: FBG trends from Week 1 to Week 15; B: Comparison of NA levels between groups at Week 10 and Week 14. (***: P < 0.001)

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  Fig. 5. Trends and intergroup comparisons of FBG levels from Week 15 to Week 18. (*: compared to Untreated Group, P < 0.05)

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  Fig. 6. The architecture of the stellate ganglion was measured using four quadrants of each section (a-d), and the average measurement was recorded. The negative control group exhibited normal nerve cells with uniform architecture (A), while the positive control group (B) and treatment group (C) showed minimal shrinkage of nerve cells. In contrast, the untreated group exhibited obvious nerve atrophy characterized by a reduction in ganglionic size (D). The representation (A-D) was depicted in a bar graph, with the untreated group (D) showing significantly greater shrinkage compared to the positive control and treatment groups (***p < 0.005) (X400)

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  Fig. 7. Negative control (A) shows preserved vascular architecture with intact endothelium, well-organized elastic lamellae, and normal smooth muscle cells; Positive control (B) demonstrates moderate preservation of smooth muscle cells with cytoplasmic clearing and mild structural alteration; MCC950-treated group (C) exhibits minimal disruption of the endothelial layer and improved smooth muscle cell integrity compared with the untreated group;Untreated group (D) exhibits intimal endothelium breakdown (red arrow), cytoplasmic clearance of smooth muscle cells (blue arrow), and sub-medial separation (yellow arrow), indicating significant endothelial damage (×400)

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  Fig. 8. The qualitative analysis of the Masson trichrome staining revealed the least collagen deposition in the negative control group (A), observed in the endocardium, perivascular area, and myocardium. Although there was similar blue staining intensity in both the positive control (B) and treatment group (C), the intensity of staining (red arrow) was markedly more evident in the untreated group (D) (X400)

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  Fig. 9. The cross-sectional area of each cardiomyocyte within a focused microscopy area was measured by averaging the length (measured along the blue line) and width (measured along the red line). The negative control group (A) exhibited normal cardiac tissue. Increasing evidence of cardiomyocyte atrophy was observed in the positive control (B), treatment (C), and untreated group (D), respectively. However, these changes were not statistically significant (E) (X400)