Effects of thymalin and α-tocopherol on morphofunctional state of neuroendocrine system at the early stages of atherogenesis

Abstract

The effects of thymalin and ~-tocopherol on the morphofunctional state of hypothalamohypophyseal neurosecretory system, thyroid gland, and adrenals at the early stages of atherogenesis are described. Correction of pathological changes in the neuroendocrine organs was accompanied by restoration of lipid homeostasis, decrease in intensity of lipid peroxidation, prevention of progressive atherosclerotic alterations in major arteries. Key Words: thymalin; o:-tocopherol; atherosclerosis; neuroendocrine system; thyroid gland; adrenalsThe hypothalamohypophyseal neurosecretory system (HHNS) is a key component of neuroendocrine regulation of lipid homeostasis [2,10]. A correlation has been established between functional state of HHNS during hyperlipoproteinemia and the degree of pathological changes in the microcirculatory bed and major arteries [3,4,6]. The HHNS-produced hormone vasopressin has immunomodulating properties and participates in formation of immunological status [9]. An important role in pathogenesis of atherosclerosis is played by disorders in the function of endocrine glands [5,8]. The state of neuroendocrine system during hyperlipoproteinemia is most certainly affected by activation of lipid peroxidation and decreased antioxidant activity.We compared the effects of a thymus hormone thymalin and ~-tocopherol on the morphofunctional state of HHNS, thyroid gland, and the adrenals at the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 45 male Chinchilla rabbits weighing 2.5-3.0 kg. Group 1 rabbits (control) Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow were maintained on the standard diet. Group 2 rabbits were given 0.3 g/kg body weight cholesterol during a 2-month period (atherogenic diet model according to N. N. Anichkov). Group 3 rabbits were injected with intramuscular thymalin (0.25 mg/kg) during 10 days on month 2 of the diet. Similarly, group 4 rabbits were injected with ~-tocopherol (50 mg/kg).In serial brain slices the hypothalamic supraoptic (SO) nuclei and neurohypophysis were studied by the methods of Gomori--Maiorova, Nissl, and Milenkov. The functional state of HHNS was accessed according to [7], taking into account the amount of gomori-positive substance in the neurosecretory cells, hypothalamohypophyseal tract and neurohypophysis. The percentage of "bright" and "dark" cells was counted in the SO nuclei, as well as the amount of pyknomorphous cellular elements. The value of neuronal nucleus and soma areas were determined a Leitz-ASM semiautomatic image analyzer. Structural changes in endocrine glands were revealed by staining with hematoxylin and eosin according to Goldman, Mallory, and van Gieson. The mass indices of thyroid and adrenals were determined, and the index of atherosclerotic damage (lAD) to the aorta [1] was used to access the severity of atherosclerotic process. Lipoprotein (LP) fractions and malonic dialdehyde were determined in serum using conventional techniques.

Changes in cerebral vessels during experimental hyperlipidemia

“…Thus, after 4 months of atherogenic diet cerebral arteries of different diameter showed initial manifestations of atherosclerosis such as lipid deposition in different structures of the arterial wall and functional changes in the endothelium. According to previous classification, the former are specific for HLP, while the latter are nonspecific [4,5,8,9]. Lipid depositions in the vascular lumen, endotheliocytes, myocytes, subendothelial layer, pericytes, and perivascular astrocytes were discovered in cerebral arteries of a different diameter.…”

“…Elevated content and enhanced transport of blood lipoproteins through the vascular wall affect both large arteries and microcirculatory vessels (MCV) of different organs [3,5]. Diffuse microcirculatory disturbances in the myocardium, liver, lungs, kidney, and other organs, the earliest manifestations of experimental hyperlipidemia (HLP), are considered to be the microangiopathy of lipid origin preceding pathological changes in large arteries (lipid strips and spots, fibrous plaques, and others) [2,4,5,[7][8][9]. Morphological changes in large cerebral vessels and MVB at the early stages of HLP have not been studied.…”