The pathogenesis of and susceptibility to malabsorption syndrome in broilers is associated with heterophil influx into the intestinal mucosa and epithelial apoptosis.

Malabsorption syndrome (MAS) in broilers is characterized by enteritis and reduced body weight gain. The pathogenesis of the intestinal lesions and the reasons for susceptibility differences between broiler lines are not clear. We studied the development of enteric lesions, epithelial apoptosis, and cell proliferation in relation to susceptibility. One-day-old chickens from two broiler lines were orally inoculated with intestinal homogenate derived from MAS-affected chickens. Vacuolar degeneration and apoptosis of the villous epithelium and infiltration of heterophils into the lamina propria occurred from day 1 post-inoculation. Following heterophil accumulation, at day 4 to 6 post-inoculation, there was severe apoptosis of the crypt epithelium and villous atrophy. The susceptible broilers had a significantly greater influx of heterophils and, subsequently, severe epithelial apoptosis and cystic damage to the crypts. There appeared to be a causal relationship between heterophil influx and the onset of apoptosis. Coincident with the epithelial apoptosis, MAS-affected chickens had crypt hyperproliferation and faster epithelial turnover. Heterophil infiltration and epithelial apoptosis appear to be critical in the pathogenesis of MAS. Heterophil recruitment may be a major factor in differences in susceptibility to MAS.     

HISTOLOGICAL STUDY OF MUSCULAR CHANGES IN PROGRESSIVE MUSCULAR DYSTROPHY

Changes of skeletal muscle of 28 patients with progressive muscular dystrophy were studied light microscopically. Slowly progressive muscular atrophy with various forms of degeneration and more acute necrosis with incomplete regeneration were the principal changes. Fatty tissue infiltration and fibrosis of the interstitial tissue seemed to occur relatively late in the course of the disease. Incidence of necrosis and regeneration of muscle fibers are significantly higher in the Duchenne-type dystrophy and in an early stage, thus giving some quantitative difference concerning the genetic clinical types and duration of the disease, though no definite specific change is found for each type of muscular dystrophy.
Significance of these changes are discussed from a morphological standpoint and under consideration of biological speciality of muscle fiber. Regenerative substitution of necrotic muscle fiber performed by survived nuclei of the necrotic fiber itself in close association of myophago-cytosis appeared to be a peculiar process exhibited by skeletal muscle as a syncytial cell.     

Infectious stunting syndrome of chickens in Great Britain: field and experimental studies

Field cases of infectious stunting syndrome, and experimental cases produced by inoculating 1-day-old chicks with intestinal homogenates obtained from field cases, were studied. In the intestines of stunted 4- to 6-day-old chickens there was degeneration and necrosis of enterocytes in the crypts of Lieberkuhn and an infiltration of macrophages and lymphocytes into the lamina propria. Some crypts were distended with necrotic and degenerating cells, including heterophils, and there was hypertrophy of enterocytes in the crypts and zones of maturation. The proximal jejunum was more severely affected than other sections of the small intestine, and up to 25% of the crypts were involved. Cold stress increased the severity and extent of these intestinal lesions at 5 days of age. In chickens more than 8 days of age there were a few cystic crypts lined by cuboidal to squamous epithelium, and an apparent loss of crypts. Necrosis and degeneration of epithelial cells lining pancreatic ducts and ductules were observed in 9% of field cases aged 4 to 6 days and 2% of experimentally infected chickens at 5 days of age. Pancreatic degeneration was noted in 35% of field cases aged more than 13 days of age, but in only 0.75% of experimentally infected cases at 14 days of age. Five-day-old experimentally infected broiler chickens had a greater intestinal length per unit live-weight than controls, and they also had a greater intestinal weight per unit length. In field cases, the greatest intestinal length per unit live-weight was in severely stunted chickens with pancreatic degeneration. Osteodystrophy was a frequent, but not consistent, feature in poorly grown birds in many broiler flocks over 2 weeks of age which had infectious stunting syndrome, but it was not prominent in experimental cases.     

Equine cutaneous mastocytoma: morphology, biological behaviour and evolution of the lesion.

Thirty equine cutaneous mastocytomas were examined histologically and two were studied ultrastructurally. Lesions were characterized by distinct sheets of well-differentiated mast cells with variable degrees of eosinophil infiltration, collagen degeneration, necrosis, granulomatous inflammation and fibrosis. Twenty-two of 25 growths did not recur for up to 6 years after surgical excision, two recurred at the surgical site and one spontaneously regressed less than 3 months after obtaining a biopsy sample. Equine cutaneous mastocytoma is a benign proliferative lesion which seldom recurs after excision. The varied histological presentation of equine mastocytoma can be attributed to a sequence of events initiated by a cutaneous mast cell proliferation. It is suggested that these mast cells release chemotactic factors for eosinophils which accumulate and degranulate, initiating collagen degeneration and cellular necrosis with subsequent granulomatous inflammation and fibrosis. The focal spontaneous nature of the primary mast cell proliferation is typical of neoplasia.     

Cardiac lesions in broilers which died without clinical signs

Fifty-four broiler chickens that suddenly died without clinical signs or gross lesions were examined histopathologically. Histologically arteriolosclerotic changes with mainly a proliferation of intimai smooth muscle cells of the small coronary arteries (52 cases, 96.2%) and myocardial necrosis or myocardial scarring (40 cases, 74.1%), were recognized. Both changes were found mostly in the deep or intermediate layer of myocardium of the left ventricle. Topographical analysis revealed in 26 cases an accompanying myocardial necrosis in a closely related area. The cause of myocardial necrosis in the remaining eight cases was not determined except in six broiler chickens with a coronary obliterating arteritis.     

Attenuation of folic acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells.     

Endothelial injury in internal organs of University of California at Davis line 200 (UCD 200) chickens, an animal model for systemic sclerosis (Scleroderma)

Systemic sclerosis (SSc) is a multisystem disorder characterized by mononuclear cell infiltration and fibrosis. Using skin samples from human SSc and UCD 200 chickens, which spontaneously develop a hereditary disease closely resembling human SSc, we have shown previously that endothelial cell apoptosis is a primary event in the pathogenesis of SSc. The aim of the present study was to investigate the initial disease stage in visceral organs of UCD 200 chickens with special emphasis on endothelial apoptosis, mononuclear cell infiltration and collagen deposition using tissue samples from oesophagus, lung, heart, kidney and liver. Apoptotic endothelial cells were detected by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling (TUNEL), mononuclear cell infiltrates were stained with hematoxylin and eosin, and increased collagen deposition was demonstrated by Goldner staining. Apoptotic endothelial cells were detected in oesophagus, lung and kidney of UCD 200 chickens at the initial stage of the disease. No apoptotic endothelial cells were found in heart or liver of UCD 200 or in visceral organs of healthy normal UCD 058 control chickens. Oesophagus of UCD 200 chickens, which was the most affected internal organ, showed mononuclear cell infiltrations and increased deposition of collagen. Perivascular inflammatory infiltrates and collagen deposition appeared later than endothelial cell apoptosis. These data support the hypothesis that endothelial cell apoptosis initiates the disease process, followed by mononuclear cell infiltration and fibrosis.     

Pathological changes in broiler chickens fed ochratoxin A and inoculated with Escherichia coli.

A study was conducted to evaluate the effects of ochratoxin A (OA) on Escherichia coli-challenged broiler chickens. One hundred and eighty-four one-day-old broiler chicks were divided into two groups of 92 chicks each, with one group fed a control mash diet and the other fed a mash diet containing 2 parts/10(6) OA. On day 14, each group was further subdivided into two groups with one group inoculated with E. coli O78 (1 x 10(7) colony-forming units/0.5 ml) by the intraperitoneal route, whereas the other group was not inoculated with E. coli. Four birds from each group were sacrificed at 1, 2, 3, 5, 7, 10, 14 and 21 days post-inoculation to record pathological changes in the liver, kidneys, heart, lungs, bursa, spleen and thymus. E. coli infection induced perihepatitis and pericarditis in the liver and heart, respectively, in chickens infected with E. coli alone or in OA-fed birds from 1 day post-infection (DPI) onwards. At 1 DPI, a thin fibrin layer covered the liver and heart; however, at subsequent days, the layer became thicker. E. coli infection did not produce appreciable changes in the kidneys, bursa or thymus. However, there was congestion of the lungs along with mononuclear cell infiltration. Ochratoxin feeding induced changes from 10 DPI onwards in chicks fed OA alone and those infected with E. coli. The changes in kidneys included swollen proximal convoluted tubules, degeneration of tubular epithelium and interstitial nephritis. Degenerative changes and mononuclear cell infiltration were recorded in the liver. There was atrophy of the lymphoid organs along with depletion of lymphocytes. Gross and histopathological changes were more severe in chickens fed OA and inoculated with E. coli than the chickens fed OA alone or those infected with E. coli, indicating combined action of these two.     

Ultrastructural changes in nutritional cardiomyopathy of protein-calorie malnourished rats.

In this investigation, the ultrastructural features of the nutritional cardiomyopathy of protein-calorie-malnourished rats were examined. Protein-calorie malnutrition was induced in young rats by feeding them a low-protein diet (4% protein) for 6 weeks. Control animals were fed a high-protein diet (16% protein). The deficient rats showed severe restriction of body-weight gain, fatty liver and hypoproteinaemia. The results of the present study clearly demonstrated that the experimentally induced protein-calorie malnutrition brings about striking morphological changes in the heart of the rat. On light microscopy hyalinization an vacuolization of muscle fibres, loss of cross striations and myofibrils, small foci of necrosis, interstitial fibrosis and mononuclear-cell infiltration could be detected. The ultrastructural lesions were characterized by myofibrillar degeneration, contraction-band formation, dilatation of sarcoplasmic reticulum, mitochondrial swelling, dehiscence of intercalated discs, and widened interstitial spaces, especially around vessels, due to oedema fluid and cellular infiltration by mononuclear cells an activated fibroblasts with collagen fibres and microfibrils. In addition, an increase in relative heart weight was also observed. The potential role of catecholamines in the pathogenesis of this cardiomyopathy is discussed.     

Bidirectional roles of skeletal muscle fibro-adipogenic progenitors in homeostasis and disease

Sarcopenia and myopathies cause progressive muscle weakness and degeneration, which are closely associated with fat infiltration and fibrosis in muscle. Recently, experimental research has shed light on fibro-adipogenic progenitors (FAPs), also known as muscle-resident mesenchymal progenitors with multiple differentiation potential for adipogenesis, fibrosis, osteogenesis and chondrogenesis. They are considered key regulators of muscle homeostasis and integrity. They play supportive roles in muscle development and repair by orchestrating the regulatory interplay between muscle stem cells (MuSCs) and immune cells. Interestingly, FAPs also contribute to intramuscular fat infiltration, fibrosis and other pathologies when the functional integrity of the network is compromised. In this review, we summarize recent insights into the roles of FAPs in maintenance of skeletal muscle homeostasis, and discuss the underlying mechanisms regulating FAPs behavior and fate, highlighting their roles in participating in efficient muscle repair and fat infiltrated muscle degeneration as well as during muscle atrophy. We suggest that controlling and predicting FAPs differentiation may become a promising strategy to improve muscle function and prevent irreparable muscle damage.     

Expression of transforming growth factor-beta 1 and its relation to endomysial fibrosis in progressive muscular dystrophy.

Progressive muscular dystrophy is characterized by muscle fiber necrosis, regeneration, and endomysial fibrosis. Although absence of dystrophin has been known as the cause of muscle fiber degeneration, pathogenesis of interstitial fibrosis is still unknown. Transforming growth factor-beta 1 (TGF-beta 1) induces accumulation of extracellular matrix in various diseases, such as liver cirrhosis and interstitial pneumonitis. To investigate its function on the pathogenesis of progressive muscular dystrophy, it was necessary to determine the degree of TGF-beta 1 expression and the site of TGF-beta 1 immunoreactivity. In Duchenne muscular dystrophy and most of Becker muscular dystrophy, high TGF-beta 1 immunoreactivity expressed on muscle fibers and extracellular space. In other myopathies with endomysial fibrosis, however, TGF-beta 1 was seldom observed. We also examined the immunoreactivity of the latent TGF-beta binding protein, which is bound to the TGF-beta precursors. In all Duchenne muscular dystrophy and half of Becker muscular dystrophy cases, high latent TGF-beta 1 binding protein immunoreactivity was seen, but in other myopathies its immunoreactivity was seldom seen on muscle fibers or extracellular space. Therefore TGF-beta 1 may play an important role in synthesis and accumulation of extracellular matrix in progressive muscular dystrophy.     

Immunohistochemical examination of plexiform-like complex vascular lesions in the lungs of broiler chickens selected for susceptibility to idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance, and by extensive vascular remodelling. In human IPAH patients, remodelling of the pulmonary vasculature results in the formation of plexiform lesions in the terminal pulmonary arterioles. Various molecules are expressed in the human plexiform lesions, including alpha smooth muscle actin, von Willebrand factor, vascular endothelial growth factor, vascular endothelial growth factor receptor type 2, hypoxia inducible factor-1α, survivin, tenascin, collagen, fibronectin, and various immune/inflammatory cells such as, cytotoxic lymphocytes, B lymphocytes, MHC class II cells, and monocytes/macrophages are also present. Plexiform lesions rarely develop in the lungs of laboratory animals, but plexiform-like complex vascular lesions (CVL) do develop spontaneously in the lungs of broiler chickens from an IPAH-susceptible line. To examine angioproliferative and immune-system-related activities associated with CVL in broiler lungs, paraformaldehyde-fixed, paraffin-embedded lung sections from 8-week-old to 24-week-old broiler chickens were stained immunohistochemically using monoclonal or polyclonal antibodies specific for angioproliferative molecules and immune/inflammatory cells. The CVL in the lungs of broiler chickens exhibited positive staining for both angioproliferative molecules and immune/inflammatory cells. These observations combined with the close histological resemblance of broiler CVL to the plexiform lesions of human IPAH patients further validates chickens from our IPAH-susceptible line as an excellent animal model of spontaneous plexogenic arteriopathy.     

The pathology of a cricopharyngeal dysphagia

The paper describes the changes in the cricopharyngeal muscle in seven cases of dysphagia resulting from obstruction at this level which was relieved by myotomy. Histological features included degeneration and regeneration in the muscle fibres with interstitial fibrosis which was severe in some of the cases. It is considered that this restrictive fibrosis is the cause of the dysphagia and that it is secondary to muscle fibre damage, the cause of which is at present obscure. Minor degrees of muscle damage and regeneration were seen rarely in controls and fibrosis was never present. There was no evidence of underlying vascular or neurological disease in six cases; the seventh had a previous history of scleroderma but this was not thought to be the cause of the cricopharyngeal lesion. The age incidence ranged from 1 to 5 years at the onset of dysphagia; in six of the seven it was 50 years or more.     

Heliotrine poisoning of broiler chickens: an experimental clinicopathologic study of low dose intoxication

Poisoning of 7-day-old broiler chickens with a low dose of heliotrine (10 mg/kg/day for 3 days) produced retarded rate of growth in male and female birds for a period of 14 to 21 days. Liver lesions in the majority of birds were not apparent grossly and were minimal microscopically. There was no biochemical evidence of hepatic dysfunction. Microscopic lesions consisted of slight swelling of hepatocytes and enlargement of hepatocyte nuclei and occasional haemorrhage. Ultrastructural examination revealed hepatic perisinusoidal fibrosis for a period of 4 to 21 days in association with minimal morphological hepatocyte change. Some birds developed ascites and more obvious liver lesions but degeneration, necrosis or megalocytosis of hepatocytes was not a feature. It was concluded that retardation of growth rate was not due to hepatic dysfunction.     

Progressive interstitial collagen deposition in Coxsackievirus B3-induced murine myocarditis.

Myocardial fibrosis can be produced in certain inbred strains of mice after coxsackievirus B subtype 3 (CVB3) infection. The mechanism responsible for this interstitial matrix alteration is unknown. The presumption is that fibrosis occurs in areas of myocyte damage and inflammation associated with viral infection, analogous to scar formation after cell injury in other organ systems. To test this hypothesis, we examined the hearts of A/J strain mice infected with three CVB3 variants (Crowell [CVB3-CR], Woodruff [CVB3-WD], and Lerner [CVB3-LR]), each known to cause different degrees of acute myocardial injury. With these three variants, virus was present in the heart until day 28 after inoculation but was absent thereafter. Fourteen days after inoculation, inflammation with myocyte necrosis was seen in discrete foci throughout the myocardium with all three variants. Collapse and disorganization of the usually delicate connective tissue matrix identifiable by silver impregnation was seen in these areas of myocyte injury. Persistent, diffuse lymphocytic infiltration of the myocardium was seen 55 days after inoculation with CVB3-WD and CVB3-LR, but hearts initially infected with CVB3-CR showed only rare interstitial lymphocytes comparable to uninfected control hearts. The focal scars produced by myocyte necrosis 14 days after inoculation were accentuated and heavily collagenized 55 days after inoculation with CVB3-WD and CVB3-LR; however, these foci were indistinct 55 days after inoculation with CVB3-CR. Furthermore, the usually delicate network of interstitial collagen fibers surrounding individual myocytes became thickened throughout the heart 55 days after inoculation with CVB3-WD and CVB3-LR, away from visibly scarred areas produced early after infection with these variants. This diffuse reticulin thickening was not seen after infection with the Crowell variant. Only the virus variants associated with persistent interstitial inflammation at day 55 developed major collagen matrix alterations and interstitial fibrosis. We conclude that this persistent interstitial lymphocytic infiltration reflects altered immune function related to specific virus variants in this animal strain. We postulate that these lymphocytes are part of a delayed immunopathogenic response uncoupled from the original viral injury and inflammatory damage. Potential mechanisms by which this interstitial lymphocytic infiltration results in fibrosis are discussed.     

Anatomo-pathologic findings in 25 autopsy cases of AIDS

Pathologic findings in 25 autopsies of AIDS. The common and severe changes of the central nervous system, lungs, adrenals, heart, kidneys and gonads are reviewed in a series of autopsies of AIDS. In the brain, HIV infection induces directly inflammatory infiltrates including the typical multinucleated giant cells described by Sharer. In addition, primary lymphomas are seen as well as reactive and inflammatory lesions that are caused by opportunistic infections, such as those of poliomavirus, Cytomegalovirus and Toxoplasma gondii. In the lung, interstitial inflammation prevails, which may be related to direct HIV infection and include rare multinucleated giant cells like the ones described by Sharer. Opportunistic infections are often associated, and are commonly sustained by Cytomegalovirus and Pneumocystis carinii. A peculiar findings is the evolution from septal inflammation to fine fibrosis and hyaline degeneration, either focal or diffuse. We believe that the severe respiratory insufficiency that is commonly seen in the advanced stages of AIDS could be related to the interstitial damage. In the adrenal gland, the most common change is Cytomegalovirus infection affecting both the cortex and the medulla, and inducing massive necrosis in the cortex with little or no reaction. Again, adrenal involvement should be related to adrenal functional insufficiency, which may be over-looked clinically because of the preponderant lesions of other sites. In the heart, myocarditis is often discrete, and may be complicated by perivascular fibrosis and rare foci of myocytolysis; in some cases primary lymphomas may also develop. In the kidney, several histological lesions are found, including glomerular damage with segmental necrosis, cortical areas of hyporeactive necrosis, and mild interstitial inflammation. In the gonads, the changes are partly induced by drug abuse, and consist of atrophy with secondary hypoplasia of the germ cells and interstitial fibrosis. In conclusion, the most important abnormalities consist of opportunistic infections, hyporeactive necrosis, fibrotic evolution of the inflammatory infiltrates and neoplasias (Kaposi's sarcoma and lymphomas). In this work, the changes of the lymphoid organs are only mentioned, for they have been widely reviewed elsewhere.     

Idiopathic hepatic fibrosis with cholestasis in broiler chickens: Immunohistochemistry of hepatic stellate cells

Immunohistochemical examinations of hepatic stellate cells (HSCs) were performed on six enlarged livers from broiler chickens with malformation of the extrahepatic biliary tract (group 1) and on eight broiler livers affected with naturally occurring cholangiohepatitis without biliary malformation (group 2). The livers from both groups were grossly enlarged, firm and tan-coloured, and histologically revealed severe diffuse fibrosis with proliferation of bile ductules. HSCs positive for muscle actin and desmin actively proliferated in the perisinusoidal space and around newly formed bile ductules. There was no difference in the immunohistochemical reactivities and location of HSCs between the two groups. The findings suggest that the diffuse hepatic fibrosis found in group 2 as well as group 1 results from reactive proliferation of HSCs.     

Experimental transmission of hydropericardium syndrome and protection against it in commercial broiler chickens

Liver collected aseptically from broiler chickens suffering from natural outbreaks of hydropericardium syndrome was homogenised in phosphate buffered saline (1:5) or normal saline (1:10). A dose of 0.25 ml of 800 g supernatant (inoculum S) in the first case or homogenate without centrifugation (inoculum T) in the second case was injected subcutaneously into 12- to 15-day-old broiler chickens. Lesions similar to natural outbreaks of the syndrome appeared in 2 to 5 days. Inoculum S inactivated with 0.1% formalin for 24 h (Vac S) or inoculum T inactivated with 0.5% formalin for 72 h (Vac T) was injected into commercial broiler chickens at 10 or 15 days of age. The birds were challenged with inoculum S or inoculum T at 20 or 25 days of age. Experimentally both vaccines gave satisfactory protection, but under field conditions, Vac T was superior.     

甘草酸二铵对肝纤维化大鼠肝脏脂质过氧化与间质性胶原酶活性的影响

目的：探讨甘草酸二铵影响纤维化肝脏脂质过氧化与间质性胶原酶活性的抗肝纤维化作用机制。 方法： 以四氯化碳(CCl4)皮下注射与高脂肪低蛋白饮食复合因素诱导大鼠肝纤维化模型，而后予以甘草酸二铵口服治疗，正常大鼠与模型对照组给予等量生理盐水。HE染色与胶原染色观察大鼠肝组织炎性坏死与胶原沉积病理改变，按试剂盒方法检测血清肝功能（ALT、AST、Alb与总胆红素等）变化，检测肝组织主要过氧化损伤指标：超氧化物歧化酶（SOD）活性, 丙二醛（MDA）含量，谷胱甘肽（GSH）含量与谷胱甘肽过氧化物酶（GSH-Px）活性，水解法测定肝组织羟脯氨酸含量，酶底物反应法分析肝组织间质性胶原酶活性变化，RT-PCR法分析肝组织Ⅰ型前胶原基因表达。 结果： 与正常大鼠相比，模型大鼠肝脏有明显胶原沉积与肝纤维化，伴有不同程度的肝细胞炎性损伤坏死；甘草酸二铵药物组明显减轻模型大鼠肝组织损伤坏死与胶原沉积等病理变化。模型大鼠肝功能指标,包括血清总胆红素含量、ALT与AST活性、白蛋白含量均明显减少（P<0.01）。药物组大鼠血清总胆红素含量、AST与ALT活性显著低于模型组（P<0.05），而白蛋白含量高于模型组（P<0.05）。此外，药物组大鼠肝组织羟脯氨酸含量(151.3±37.3 μg/g)明显少于模型组(170.9±15.3 μg/g，P<0.05)，Ⅰ型前胶原基因表达弱于模型组（P<0.05）；肝组织MDA含量(1.96±0.23 μmol/g)低于模型组(2.44±0.32 μmol/L, P<0.05)，SOD水平(19.60±0.97 NU/g)高于模型组(20.60±0.33 NU/g，P<0.05)，GSH含量(47.0±9.1 g/g)与GSH-Px活性(53.1±4.1 U/g)高于模型组(41.2±3.5 g/g；46.7±6.1 U/g，P<0.05)；肝组织间质性胶原酶活性(43.89±7.74 U)高于模型组(32.01±2.75 U，P<0.05)。 结论： 甘草酸二铵有明显抗肝纤维化大鼠肝脏脂质过氧化损伤与提高肝组织间质性胶原酶活性的作用，该作用是药物抗肝纤维化的重要机制。     

PATHOLOGY OF EXPERIMENTAL RADIATION PANCARDITIS I.

Radiation-induced heart injuries were morphologically studied by using the rabbits irradiated with a single dose of 3,000R (group I) or 300R of X-ray group II) from 1 hour until 6 months. There was no essential difference in the lesions of the hearts from group I and that of group II. Acute epicarditis was found as early as 1 hour after irradiation and it became maximum in severity at 1-2 days. In the myocardium, there were degeneration and resolution of the myocardial cell, various architectural changes of mitochondria, and disorganization of the intercalated disc. Polymorphonuclear cell infiltration and endothelial injuries of the capillaries occurred in the interstitial tissue. In addition, endocarditis with or without thrombus formation was often found. Acute inflammation was seen in the myocardium of group II rather later than that of group I, but it disappeared earlier. In the later stage, fibrosis finally occurred in the epicardium and endocardium. Glycoprotein degeneration of the muscle cells and fibrosis appeared in the myocardium. The pathogenesis of radiation pancarditis is thought to be dependent not only on the disturbance of microcirculation caused by endothelial cell damage of the capillaries, but also on alterations of the myocardial mitochondria as a result of direct injury.